bims-carter Biomed News
on CAR-T Therapies
Issue of 2026–04–19
sixty papers selected by
Luca Bolliger, lxBio
  1. Harnessing the Power of CAR-NK Cells for Solid Tumors: Challenges, Innovations, and Future Frontiers in Immunotherapy.
  2. CAR-T cells in solid tumors: engineering, biomarkers, translational pathways and the road ahead.
  3. Regulatory T cells in the era of cell and gene therapy: biology, clinical translation, and future prospects.
  4. Chimeric antigen receptor T cells for autoimmune diseases, in particular immune thrombocytopenia.
  5. Realizing the promise of CAR-T cell therapies for autoimmune diseases.
  6. Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells.
  7. CAR-NK Cell Biology and Engineering for Solid Tumors, With a Focus on Lung Cancer.
  8. Autologous CD19/BCMA CAR-T cell therapy for myasthenia gravis: Advancing care for those with severe disease.
  9. CAR Treg therapies for neurodegenerative diseases.
  10. CLO26-108: Efficacy of CAR T Cell Therapy in Extranodal and Nodal Large B-Cell Lymphoma.
  11. Implementing the EU HTA regulation and joint clinical assessment: a multi-stakeholder perspective from Italy.
  12. Editorial: Innovations in development, translational research and manufacturing of CAR T cells.
  13. Allogeneic CD19 CAR T cells armed with an anti-rejection CD70 CAR overcome antigen escape and evade alloimmune responses.
  14. A new therapeutic frontier: CD19-targeting CAR-T cell therapy in rheumatoid arthritis: a concise report.
  15. Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.
  16. Unlocking the potential of T cell engagers in solid tumors.
  17. Human Cytomegalovirus Infection in Haematopoietic Stem Cell Transplant Recipients and CAR T Cell Recipients - PART 1: Risk Factors, Clinical Impact and Immune Response.
  18. Engineering TCR-directed T-cells for the treatment of multiple myeloma.
  19. Don't Cut the Cord: Why Umbilical Cord Blood Still Deserves a Place in Transplantation.
  20. Exosomes and Extracellular Vesicles in CAR-T Cell Therapy: Emerging Mediators and Biomarkers of Cardiac Injury.
  21. Advances in predicting T cell epitope recognition for cancer immunotherapy.
  22. Thailand's Emerging Role in the Cell and Gene Therapy Revolution: A Review of Progress and Potential.
  23. Novel immunotherapies for prostate cancer.
  24. Democratizing the Cure: Indigenous Innovations and the Future of Pediatric Cell and Gene Therapy in India.
  25. Case Report: Transverse myelitis following CAR-T cell therapy for post-transplant lymphoproliferative disorder.
  26. Isolation, Cultivation, and Transient Transfection of Primary Human T Cells to Generate Chimeric Antigen Receptor (CAR) T Cells.
  27. Synergizing immunity: lipid nanoparticle-mediated mRNA and gene delivery as a next-gen paradigm in cancer immunotherapy.
  28. Immunotherapy for pediatric solid tumors: overcoming biological barriers through rational multimodal combinations.
  29. A decade of innovation in healthcare: Automation, bio-printing and digital twin technologies for personalized therapies.
  30. Reviving CD2 signaling to boost CAR T-cell therapy.
  31. Ontology-driven generation of parameters for health technology assessment models: A prompt engineering study.
  32. Bayesian quantitative decision-making framework in cell and gene therapy development for rare diseases.
  33. Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.
  34. Data-informed optimization of CAR T-cell therapy long-term follow-up.
  35. "Beyond Efficiency: Reimagining Health Technology Assessment in the Age of Artificial Intelligence".
  36. Emerging advantages of nano delivery systems in enhancing CAR-T/CRISPR-Cas9 mediated cancer therapeutics.
  37. Federated, governed, and interoperable? The emerging architecture of public human genomic data infrastructures: a European perspective.
  38. [The regional network for CAR-T therapies in the Lazio Region: a governance model for innovation and sustainability.]
  39. Precision oncology in the age of AI: lessons from AI-driven drug discovery and clinical translation.
  40. Therapeutic Alternatives to Recombinant Biologics: Mechanistic Framework, Clinical Evidence, and Selection Guidance.
  41. Clinical innovations and future directions of nanoparticles in the treatment of psychiatric and neurological disorders.
  42. Streamlining regulation to Unlock Digital Health Innovation in the NHS.
  43. Viral Reactivation in Multiple Myeloma Patients Receiving Anti-BCMA Chimeric Antigen Receptor T-Cell Therapy.
  44. Determinants of willingness to share personal genomic data: a systematic review focused on health literacy.
  45. Italian Medicines Agency's reform and time until pricing and reimbursement decisions: a time-to-event analysis.
  46. [Bispecific T-cell engagers for the treatment of autoimmune diseases: Current status and therapeutic perspectives].
  47. Governing the rise of AI in healthcare: A comparative governance document and implementation implications across five jurisdictions.
  48. Virus-directed CAR immunotherapies for chronic HBV and HIV: a systematic synthesis of preclinical and early clinical evidences.
  49. Disruptive innovation in breast cancer therapeutic development.
  50. Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.
  51. Cytokine-based NK cell engineering for cancer immunotherapy.
  52. Landscape of T-Cell Engagers in Solid Tumors.
  53. Nanoparticle-mediated mRNA delivery for cancer, autoimmunity, and genetic diseases: a rapid review.
  54. The status of cell and gene therapy education in medical schools-An international survey.
  55. Advancing FDA New Approach Methodologies from animal models through digital twins.
  56. The regulatory landscape for extracellular vesicle therapies: Australian context and future directions.
  57. Phenotypic response surface-guided pharmacotherapy for personalized combination treatment in complex diseases.
  58. Advancing Public Health Through Internationally Coordinated Medical Device Registries Comment on "Quality and Utility of European Cardiovascular and Orthopaedic Registries for the Regulatory Evaluation of Medical Device Safety and Performance Across the Implant Lifecycle: A Systematic Review".
  59. Familial and genetic overlap between Sjögren's disease and other autoimmune diseases.
  60. Trial-Based Economic Evaluations Conducted alongside Studies Embedded in Australian Healthcare Services and Programs: A Scoping Review.
  1. Cancer Commun (Lond). 2026 ;46 0023
    Harnessing the Power of CAR-NK Cells for Solid Tumors: Challenges, Innovations, and Future Frontiers in Immunotherapy.
    Mengchao An, Jiayao Yan, Baorui Liu, Qin Liu.
      Solid tumors remain a formidable challenge in cancer therapy, often evading even the most advanced immunotherapies. Natural killer (NK) cells, cytotoxic innate lymphocytes capable of recognizing and eliminating tumor cells without prior antigen sensitization, have emerged as a compelling alternative to T cells in adoptive cell therapy. Compared to chimeric antigen receptor (CAR)-T cells, CAR-engineered NK cells offer distinct advantages, including a substantially reduced risk of graft-versus-host disease (GvHD) and cytokine release syndrome (CRS). These features enable the development of "off-the-shelf" allogeneic cell products with improved safety and accessibility. Early clinical studies of CAR-NK cells have demonstrated encouraging efficacy in hematological malignancies alongside an excellent safety profile, fueling enthusiasm to extend this approach to solid tumors. However, the efficacy of CAR-NK cell therapy against solid tumors is limited by multiple barriers, including the immunosuppressive tumor microenvironment, poor infiltration, and persistence of NK cells in tumor tissues, heterogeneity of tumor antigen expression leading to immune escape, and the potential for NK cell dysfunction or exhaustion in chronic tumor settings. To overcome these obstacles, innovative engineering strategies are being developed. Approaches include armoring CAR-NK cells to resist tumor-induced immunosuppression, enhancing their trafficking and persistence, designing multi-antigen-targeted receptors, and incorporating built-in safety switches. This review highlights CAR-NK antitumor mechanisms, examines key challenges in solid tumor applications, and discusses cutting-edge advances and combination strategies aimed at unlocking the full therapeutic potential of CAR-NK cells. By addressing these challenges, CAR-NK cell therapy could open a new frontier in solid tumor immunotherapy.
    DOI:  https://doi.org/10.34133/cancomm.0023
  2. Front Immunol. 2026 ;17 1796675
    CAR-T cells in solid tumors: engineering, biomarkers, translational pathways and the road ahead.
    Nada Saed Homod Al Shaer, Ibraheem Masoud, Aya Tleyjeh, Attas Alawi Al-Attas, Maryam Alawi Al-Attas, Mohammed Imran Khan, Ahmed Yaqinuddin.
      Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of hematologic malignancies by enabling antigen-specific tumor targeting and durable clinical responses. However, its translation to solid tumors has been limited by fundamental biological barriers, including antigen heterogeneity, poor tumor infiltration, and profound immunosuppressive and metabolic constraints within the tumor microenvironment. These factors collectively drive CAR-T cell dysfunction, exhaustion, and limited persistence, resulting in modest and inconsistent clinical efficacy. This review provides a concept-driven synthesis of recent advances in CAR-T cell therapy for solid tumors, with a specific focus on systems-level engineering strategies that integrate tumor biology, spatial context, and cellular metabolism. We highlight emerging approaches such as in vivo CAR programming, logic-gated and multi-antigen receptor designs, and armored CAR-T cells engineered to resist immunosuppression and metabolic stress. Importantly, this review goes beyond descriptive engineering advances by emphasizing the growing role of computational modeling, artificial intelligence, and spatial multi-omics in guiding antigen selection, CAR circuit design, and predictive assessment of therapeutic responses. Unlike prior reviews that primarily summarize antigen targets or CAR engineering strategies, this review integrates biological barriers in solid tumors with emerging engineering solutions to provide a conceptual framework for the development and clinical translation of next-generation CAR-T therapies. By integrating biological determinants of failure with rational engineering solutions, the review delineates translational pathways that link mechanistic insight to clinical implementation. This review advances the field by framing CAR-T therapy for solid tumors as a systems engineering challenge rather than a single-target optimization problem. By integrating immunology, bioengineering, computational sciences, and spatial biology, we outline a roadmap for the development of safer, more durable, and context-aware CAR-T therapies. Continued progress will depend on tumor-specific antigen discovery, interdisciplinary collaboration, and scalable manufacturing and regulatory frameworks, collectively enabling the next generation of effective CAR-T therapies for solid tumors.
    Keywords:  CAR-T cell therapy; antigen heterogeneity; biomarker-driven design; immune escape; metabolic reprogramming; solid tumors; spatial omics; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2026.1796675
  3. Front Immunol. 2026 ;17 1762753
    Regulatory T cells in the era of cell and gene therapy: biology, clinical translation, and future prospects.
    Yohei Sato.
      Regulatory T cells (Tregs) play a central role in maintaining immune homeostasis. Therefore, owing to their unique immunomodulatory function, their adoptive transfer has been investigated as a novel therapeutic modality. Recent progress in cell manufacturing has allowed the application of Tregs as cell therapy products, and several are being tested in human clinical trials. Furthermore, several clinical trials are aimed at evaluating Treg modulation methods, including cytokine administration, monoclonal antibodies, Treg depletion, and adoptive Treg transfer. Among these, adoptive Treg transfer is a promising cell and gene therapy modality that is potentially beneficial for both genetic and non-genetic diseases, including autoimmunity. To determine the current trends in research on Treg-based therapies, we performed a database search and found that investigational clinical trials have been performed not only for autoimmunity but also for a wide range of diseases. In this mini review, we introduce early benchmarking Treg trials together with recent advances in research on Treg biology shown in non-genetic diseases and not just limited to autoimmunity.
    Keywords:  clinical trial; good manufacturing practice (GMP); lentiviral (LV) vector; rapamycin; regulatory T cells (Treg)
    DOI:  https://doi.org/10.3389/fimmu.2026.1762753
  4. Br J Haematol. 2026 Apr 16.
    Chimeric antigen receptor T cells for autoimmune diseases, in particular immune thrombocytopenia.
    Samuel P Soff, Samuel Ruder, James B Bussel.
      Immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impaired platelet production. Both plasma/B cell-producing anti-platelet autoantibodies and autoreactive T cells lead to thrombocytopenia and treatment refractoriness. Conventional treatments often fail to induce sustained remission off treatment (SROT). Chimeric antigen receptor (CAR) T cell therapy, developed for haematological malignancies, has recently been explored in autoimmunity to target plasma/B cells, reducing autoantibody production. Early studies suggest potential for benefit in refractory autoimmune disease, including ITP. This nutshell review summarizes CAR T cell therapy in autoimmunity, especially refractory ITP.
    Keywords:  CAR T cells; immune thrombocytopenia; immunotherapy
    DOI:  https://doi.org/10.1111/bjh.70482
  5. Nat Rev Drug Discov. 2026 Apr 17.
    Realizing the promise of CAR-T cell therapies for autoimmune diseases.
    Gwendolyn K Binder, Raphaël Ognar.
      
    DOI:  https://doi.org/10.1038/d41573-026-00062-0
  6. bioRxiv. 2026 Apr 06. pii: 2026.04.02.715976. [Epub ahead of print]
    Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells.
    Cheng-Fu Kuo, Zhen Tong, Yi-Chiu Kuo, Miso Park, Jeremy King, Kevin Ly, Bea Parcutela, Lawrence A Stern, Zhiqiang Wang, Brenda Aguilar, Renate Starr, Wen-Chung Chang, Julie R Ostberg, Daniel Rossi, Mary C Clark, Darya Alizadeh, Stephen J Forman, John C Williams, Christine E Brown.
      Chimeric antigen receptor (CAR) T cells have transformed cancer treatment, yet challenges for achieving broader clinical success remain, including overcoming tumor antigen heterogeneity and limited T cell fitness. To address these challenges and enhance CAR T cell functionality, we leveraged meditope technology, a lock-and-key platform where Fab regions of antibodies are modified to bind a small cyclic peptide termed meditope (meP). We developed a panel of meditope-enabled Fab-based CARs (meCARs), which show selective binding to the meP and comparable activity to traditional single-chain variable fragment (scFv)-based CARs. Focusing on HER2-targeted meCARs for evaluating platform utility, we exploited the modularity of the meditope platform to detect meCAR T cells using meP-fused fluorescent agents, promote meCAR T cell expansion via meP-fused IL-15 cytokine, and broaden tumor antigen targeting through meP-fused antibodies to address tumor heterogeneity. These findings establish the meditope technology as a versatile strategy to augment CAR T cell functionality and overcome key limitations of current CAR-based therapies.
    DOI:  https://doi.org/10.64898/2026.04.02.715976
  7. Cell Biol Int. 2026 Apr;50(4): e70152
    CAR-NK Cell Biology and Engineering for Solid Tumors, With a Focus on Lung Cancer.
    Xiao Lyu, Na Zhu, Ruijuan Guo, Jurbek Yuldasheyv.
      Over the past decade, chimeric antigen receptor (CAR) T-cell therapy has revolutionized cancer immunotherapy, demonstrating remarkable efficacy in treating relapsed or refractory hematologic malignancies across both pediatric and adult populations. In parallel, CAR-engineered natural killer (CAR-NK) cells have emerged as a complementary and promising alternative to CAR-T therapy, offering several inherent advantages. Unlike CAR-T cells, CAR-NK cells operate independently of major histocompatibility complex (MHC) compatibility and are associated with a lower risk of adverse immune reactions. They also provide practical benefits, such as the potential for standardized, "off-the-shelf" therapeutic formulations. Consistent and encouraging outcomes have been reported with CAR-NK cell therapy in hematologic cancers; however, their success against solid tumors remains constrained by multiple challenges, including limited tumor infiltration, suboptimal trafficking, and the immunosuppressive characteristics of the tumor microenvironment. Importantly, lung cancer presents indication-specific barriers to cellular immunotherapy, including profound inter and intratumoral heterogeneity, a highly immunosuppressive pulmonary tumor microenvironment, and a narrow safety margin in a vital organ where inflammation or edema can rapidly impair gas exchange. These factors limit the depth and durability of responses achieved with current systemic modalities in a substantial fraction of patients and also constrain adoptive cell therapy in thoracic malignancies. Therefore, lung cancer represents both a compelling and stringent setting to develop safer and more durable engineered cellular platforms such as CAR-NK cells. Lung cancer, one of the most prevalent and lethal malignancies worldwide, still depends largely on conventional treatment modalities such as surgery, chemotherapy, radiotherapy, and targeted agents. Accordingly, we organize this review around lung cancer-specific design constraints, antigen heterogeneity/escape, impaired trafficking into pulmonary tumors, an immunosuppressive lung microenvironment, and a narrow pulmonary safety window, and map each constraint to actionable CAR-NK engineering and combination strategies.
    Keywords:  CAR‐NK cell; NK cells; NSCLC; immunotherapy; lung cancer
    DOI:  https://doi.org/10.1002/cbin.70152
  8. Med. 2026 Apr 10. pii: S2666-6340(26)00039-5. [Epub ahead of print]7(4): 101036
    Autologous CD19/BCMA CAR-T cell therapy for myasthenia gravis: Advancing care for those with severe disease.
    Henry J Kaminski, Linda L Kusner.
      Ruan and colleagues report that dual-target CD19/BCMA CAR-T cell therapy produced marked clinical improvement in highly refractory myasthenia gravis, with steroid discontinuation and minimal toxicity. Beyond symptom control, deep immune profiling revealed sustained B-cell depletion, reduced autoantibodies, and systemic immune reprogramming toward a less inflammatory state.
    DOI:  https://doi.org/10.1016/j.medj.2026.101036
  9. iScience. 2026 Mar 20. 29(3): 114988
    CAR Treg therapies for neurodegenerative diseases.
    Daniel N Stein, Howard E Gendelman.
      Regulatory T cells (Tregs) promote immune tolerance by recognizing non-foreign self-antigens. Consequently, Tregs suppress chronic immune responses and prevent autoimmunity. Chimeric antigen receptor Tregs (CAR Tregs) enhance Treg responses by genetic modification for cell-specific targeting. This can lead to effective treatments for autoimmune diseases, transplant rejection, and graft-versus-host disease. An extension of CAR Tregs involves their potential ability to regulate immune responses to misfolded and aggregated proteins, which drive neurodegenerative diseases. These protein aggregates can trigger immune responses that lead to neural injury. Early preclinical and translational strategies suggest CAR Treg therapies can treat Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In each case, a Treg-based approach transforms a neurotoxic, inflammatory environment through neurotrophic responses. By doing so, CAR Tregs may restore brain balance and slow disease progression. This review highlights ongoing efforts to develop CAR Treg strategies as potential therapies for neurodegenerative disorders.
    Keywords:  Adaptive immunity; Chimeric antigen receptor; Neural homeostasis; Regulatory t cells
    DOI:  https://doi.org/10.1016/j.isci.2026.114988
  10. J Natl Compr Canc Netw. 2026 Mar 31. pii: CLO26-108. [Epub ahead of print]24(3.5):
    CLO26-108: Efficacy of CAR T Cell Therapy in Extranodal and Nodal Large B-Cell Lymphoma.
    Salman J Khan, Hamza Usman, Seemab Sheikh, Mahuri Yalamanchili.
      
    DOI:  https://doi.org/10.6004/jnccn.2025.7213
  11. Int J Technol Assess Health Care. 2026 Apr 13. 42(1): e39
    Implementing the EU HTA regulation and joint clinical assessment: a multi-stakeholder perspective from Italy.
    Michela Meregaglia, Francesco Costa, Ludovico Cavallaro, Patrizio Armeni, Monica Hildegard Otto.
       BACKGROUND: The Regulation (EU) 2021/2282 on Health Technology Assessment (HTAR), which applies as of January 2025, introduces the Joint Clinical Assessment (JCA) for selected health technologies and establishes a stakeholder network. This study aims to evaluate the expected impact of the implementation of the HTAR from a multi-stakeholder perspective, using Italy as a case study.
    METHODS: A scoping literature review was performed according to the PRISMA guidelines to inform the development of an interview guide. Target participants included Italian stakeholder representatives with an interest in the HTAR. One-on-one semi-structured interviews were conducted virtually at the end of 2024. The questions were categorized into three main topics: expected benefits and opportunities; foreseen risks or challenges; recommended actions. The interviews were transcribed verbatim and analyzed using thematic content analysis techniques.
    RESULTS: Thirteen participants included representatives from national and regional HTA bodies, health technology developers' associations, health professional associations, patient organizations, and HTA experts. The JCA is expected to enhance the quality of clinical assessment and to result in faster and more equitable access to health innovations. However, the timing will depend on the extent to which Member States require complementary analyses. Health technology developers benefit from submitting a single JCA dossier, but often cope with limited evidence and short-term deadlines. The interviewees recommended harmonizing evidence standards, investing in HTA education and training, and fostering strategic stakeholder collaborations.
    DISCUSSION: The process of harmonization induced by the HTAR is beneficial to standardize clinical assessment at the EU level, but needs to reconcile different stakeholder perspectives.
    Keywords:  HTA Regulation (HTAR); Health Technology Assessment (HTA); Italy; Joint Clinical Assessment (JCA); stakeholders
    DOI:  https://doi.org/10.1017/S026646232610364X
  12. Front Immunol. 2024 ;15 1504906
    Editorial: Innovations in development, translational research and manufacturing of CAR T cells.
    D Krones, U Koehl, H Negre, Q Rafiq, S Goldrick, M Hudecek.
      
    Keywords:  CAR NK cell therapy; CAR T cell therapy; cell therapy; haematology; immune therapy; oncology
    DOI:  https://doi.org/10.3389/fimmu.2024.1504906
  13. Nat Commun. 2026 Apr 12.
    Allogeneic CD19 CAR T cells armed with an anti-rejection CD70 CAR overcome antigen escape and evade alloimmune responses.
    Kristen Zhang, Zhe Li, Mark K O'Dair, David Qu, Adam K Mealy, Duy Nguyen, Hsin-Yuan Cheng, David Huang, Suhasni Gopalakrishnan, Zachary J Roberts, Cesar Sommer, Elvin J Lauron.
      Chimeric antigen receptor (CAR) T cells can achieve sustained clinical benefit in B cell malignancies and autoimmune diseases. Despite the many potential advantages over autologous products, allogeneic CAR T cells carry a higher risk of rejection, which may limit persistence and therapeutic efficacy. We report the design and evaluation of an optimized CD70 CAR that prevents rejection of allogeneic CAR T cells by targeting activated alloreactive lymphocytes. Co-expression of this CD70 CAR with a CD19 CAR resulted in sustained CAR T cell persistence in the presence of alloreactive lymphocytes and prolonged antitumor activity in a CD19 antigen escape model. In vivo, CD19/CD70 dual CAR T cells eliminated B cells and CD70+ T cells derived from patients with systemic lupus erythematosus in humanized mouse models, resulting in reduced immunoglobulin production. An allogeneic CD19/CD70 dual CAR T cell therapy may therefore broaden clinical applicability while enabling the use of less intensive lymphodepleting conditioning regimens prior to CAR T cell infusion.
    DOI:  https://doi.org/10.1038/s41467-026-71904-z
  14. Rheumatology (Oxford). 2026 Apr 15. pii: keag195. [Epub ahead of print]
    A new therapeutic frontier: CD19-targeting CAR-T cell therapy in rheumatoid arthritis: a concise report.
    Phillip Kremer, Isabell Haase, Johanna Richter, Ina Kötter, Dominic Borie, Boris Fehse, Nicolaus Kröger, Martin Krusche, Francis Ayuk.
       OBJECTIVES: Chimeric Antigen Receptor (CAR)-T cell therapy recently emerged as a possible new treatment option in refractory systemic autoimmune diseases (AID). With growing evidence in B-cell mediated AID, the question arises as to its potential application in difficult to treat rheumatoid arthritis (RA). Building on positive experience in a case of overlapping seropositive RA and systemic sclerosis treated with CD19 CAR-T cells at our center, we reviewed the available evidence on the efficacy and safety of CAR-T cell therapy in RA.
    METHODS: The patient successfully received a single infusion of autologous CD19 CAR-T cells (KYV-101, Kyverna Therapeutics) after lymphodepletion with fludarabine and cyclophosphamide. Clinical, serologic, and safety outcomes were monitored over 12 months, demonstrating sustained disease remission and improvement in interstitial lung disease. Furthermore, a literature review analyzed prior cases of CAR-T cell treatment in RA, focusing on patient characteristics, outcomes, and adverse events.
    RESULTS: Seven of eight previously published cases of CAR-T cell therapy in RA (7/8 ACPA positive) consistently reported significant improvement, with most patients remained stable off immunosuppressive therapy after a median follow-up of 9 months. High-grade CRS (grade 3) and ICANS (grade 4) was reported only in one patient. No serious infections were observed, even though transient hypogammoglobulinemia occurred in two patients (2/8).
    CONCLUSION: The eight reported cases highlight the potential of CAR-T cell therapy, even in patients unresponsive to B-cell-targeted treatments in RA. Larger and prospective studies are needed to assess its long-term efficacy and safety in the disease.
    Keywords:  B-cell depletion; CAR-T cell therapy; autoimmune diseases; chimeric antigen receptor T cell; cytokine release syndrome; immune- effector-cell associated neurotoxicity syndrome; rheumatoid arthritis; systemic sclerosis
    DOI:  https://doi.org/10.1093/rheumatology/keag195
  15. Nat Rev Clin Oncol. 2026 Apr 15.
    Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.
    Alaa Ali, Metin Ozdemirli, Mark P Hamilton, Michael D Jain.
      Chimeric antigen receptor (CAR) T cell therapy is now widely used for the treatment of various haematological malignancies, with emerging applications in solid tumours and autoimmune diseases. Alongside its demonstrated clinical activity, this therapeutic modality has a toxicity profile that differs from those associated with traditional cytotoxic therapies, other immunotherapies, and even other cell therapy approaches such as allogeneic haematopoietic stem cell transplantation. One increasingly recognized yet poorly understood complication is the development of post-CAR T cell therapy lymphoproliferative and lymphomatous disorders, which have a clinical and biological spectrum that remains incompletely characterized. These rare events include both CAR-transgene-positive and transgene-negative lymphomas with variable and sometimes overlapping clinical features. Causal attribution is difficult, given that these proliferations often emerge in the context of clonal haematopoiesis, inflammatory or infectious triggers, immune suppression and/or viral reactivation. In this Review, we synthesize the growing body of evidence on post-CAR T cell therapy lymphoproliferative disorders, drawing on the limited but increasing number of well-characterized cases. We outline the spectrum of lymphoproliferations described so far, highlight recurrent pathological and molecular features, and discuss factors that might promote clonal expansion or transformation, including pre-existing clonal haematopoiesis, dysregulated signalling pathways, inflammatory stimuli and, rarely, CAR-transgene vector integration. A clearer framework for these disorders might improve early recognition, guide diagnostic evaluation, support treatment decision-making, facilitate classification and consensus-building efforts, and inform future mechanistic studies and pharmacovigilance efforts.
    DOI:  https://doi.org/10.1038/s41571-026-01147-w
  16. Cancer Cell. 2026 Apr 16. pii: S1535-6108(26)00165-0. [Epub ahead of print]
    Unlocking the potential of T cell engagers in solid tumors.
    Emily Wingrove, Julie M Bailis, Anna F Farago, Jean-Charles Soria.
      T cell engagers (TCEs) represent a targeted immunotherapy approach that is reshaping the cancer treatment landscape. While multiple TCEs are approved for the treatment of patients with hematologic malignancies, TCE development in solid tumors continues to face challenges including target heterogeneity within the tumor, an immunosuppressive microenvironment, on-target toxicity in normal tissues, and complex safety profiles. Target selection, creative protein engineering, and thoughtful clinical design are core principles that will guide future strategies for the next generation of TCE therapeutics.
    DOI:  https://doi.org/10.1016/j.ccell.2026.03.011
  17. Rev Med Virol. 2026 May;36(3): e70142
    Human Cytomegalovirus Infection in Haematopoietic Stem Cell Transplant Recipients and CAR T Cell Recipients - PART 1: Risk Factors, Clinical Impact and Immune Response.
    Danya Kaplan, Emily Blyth, Gaurav Sutrave, Michelle K Yong, David J Gottlieb, Allison Abendroth, Barry Slobedman, Lauren Stern.
      Human cytomegalovirus (HCMV) is one of the most important opportunistic pathogens in immunocompromised individuals, including allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients. In allo-HSCT, HCMV seropositivity of the recipient and donor is associated with inferior survival outcomes, and post-transplant HCMV reactivation is a frequent complication, necessitating close viral monitoring and pre-emptive and prophylactic antiviral therapies. We present a review in two parts that focuses on the risk factors, immunological responses and treatment strategies for HCMV infection in allo-HSCT recipients, and also explores current evidence surrounding HCMV reactivation in recipients of chimeric antigen receptor T cell (CAR T) therapies. In the current article (Part 1), the impact of HCMV infection in allo-HSCT and CAR T cell recipients is investigated. HCMV reactivation in allo-HSCT recipients is associated with increased mortality, graft-versus-host disease (GvHD) and other microbial infections. Prominent alterations in T cell and natural killer (NK) cell recovery represent distinct immune reconstitution features associated with HCMV reactivation. Immunological biomarkers to predict HCMV complications have been proposed and their adoption in future immune monitoring strategies may allow individualised risk assessment to guide antiviral treatment decisions. The clinical significance of HCMV reactivation after CAR T cell infusion is yet to be fully determined. Continued viral surveillance and investigation of viral dynamics with correlative studies of immune function are needed in this patient population. Current and emerging strategies for treatment and prevention of HCMV complications in allo-HSCT, including use of letermovir prophylaxis and adoptive HCMV-specific T cell therapies, are explored in the following article (Part 2).
    Keywords:  CAR T; CMV; HSCT; chimeric antigen receptor; cytomegalovirus; haematopoietic stem cell transplant
    DOI:  https://doi.org/10.1002/rmv.70142
  18. Front Immunol. 2026 ;17 1755096
    Engineering TCR-directed T-cells for the treatment of multiple myeloma.
    Nida Mubin, James J Ignatz-Hoover, James J Driscoll.
      Multiple myeloma (MM) is a virtually incurable plasma cell malignancy characterized by malignant cells that expand within the tumor-permissive bone marrow (BM) microenvironment. Novel strategies are urgently needed to improve the outcomes of patients with difficult-to-treat and therapy-refractory disease. The ability to genetically manipulate T-cells and the introduction of adoptive cellular therapies (ACTs) has improved the treatment of relapsed and/or refractory (RR)MM. Emerging evidence supports the efficacy of ACTs as early lines of cancer treatment, potentially even as an alternative to autologous hematopoietic stem cell transplantation. Chimeric antigen receptor (CAR) T-cell therapies based upon genetically engineered patient-derived T-cells are utilized in routine clinical practice, however severe toxicities, therapeutic resistance, exorbitant costs, a cumbersome manufacturing process and production logistics limits their broader application. Tumor-infiltrating lymphocytes (TILs) can also mediate tumor regression and lead to durable responses, but wider efficacy is restricted by limited accessibility, reduced proliferative capacity and low effector function. In this context, autologous T-cells engineered to express T-cell receptors (TCRs) represent an intriguing option to improve MM treatment. Immunoproteasomes represent an essential cornerstone of adaptive immunity and are required for the efficient processing of antigenic peptides presented by MHC class I (MHC-I) molecules to cytotoxic CD8+ T-lymphocytes (CTLs). Recent studies have demonstrated that immunoproteasome activation increases the presentation of tumor-specific neo-antigens, thereby offering a potential strategy to improve the antimyeloma effects of T-cell-mediated immunotherapies. Here, we discuss advantages and strategies that support the administration of TCR-engineered T-cells for the treatment of MM. This review focuses on the role of immunoproteasome dependent antigen processing in shaping the myeloma immunopeptidome and enabling TCR-based immunotherapy. We discuss how modulation of neoantigen presentation may inform the design of TCR-engineered T cells and related immunotherapeutic strategies for MM.
    Keywords:  CAR T-cell; TCR-engineered T-cell immunotherapy; drug resistance; multiple myeloma; proteasome-dependent MHC class I antigen
    DOI:  https://doi.org/10.3389/fimmu.2026.1755096
  19. Int J Immunogenet. 2026 Apr 15. e70050
    Don't Cut the Cord: Why Umbilical Cord Blood Still Deserves a Place in Transplantation.
    Jenna Nunn, Kay Poulton, Robert Wynn.
      The use of umbilical cord blood (UCB) as a stem cell source in haematopoietic stem cell transplant (HSCT) has greatly declined in recent years. It has largely been replaced by mismatched unrelated and family donors, facilitated by advances in transplant technologies, including post-transplant cyclophosphamide to prevent graft-versus-host disease (GVHD). UCB remains a distinctive source of haematopoietic stem cells (HSCs) with unique immunologic and practical advantages, including for those with malignant and non-malignant diseases. Compared to other cell sources, UCB transplantation (UCBT) offers comparable survival with reduced chronic GVHD (cGVHD) and with a potent graft-versus-leukaemia (GVL) effect. These outcomes likely reflect the biology of cord-derived lymphocytes-particularly naïve, adaptable CD8+ T-cells capable of rapid differentiation and tumour-directed cytotoxicity without sustained alloreactivity. UCB permits greater human leukocyte antigen (HLA) mismatch tolerance, especially when transplant is performed T-cell replete and can be accessed immediately, reducing time to transplant for high-risk leukaemia. In addition, recent advances in ex vivo expansion technologies have overcome historical limitations of low cell dose and delayed engraftment, expanding UCB's applicability to older paediatric and adult recipients. This review discusses the evidence of using UCB as a preferred stem cell source in patients with relapsed/refractory haematological malignancies and how we may interrogate the properties of UCB to improve outcomes in these high-risk cohorts.
    Keywords:  T‐lymphocytes; cord blood; graft‐versus‐host disease; leukaemia; relapse bone marrow transplant
    DOI:  https://doi.org/10.1111/iji.70050
  20. Cardiol Rev. 2026 Apr 16.
    Exosomes and Extracellular Vesicles in CAR-T Cell Therapy: Emerging Mediators and Biomarkers of Cardiac Injury.
    Jatin Thukral, Pyush Moudgil, Ninaad Sindhwani, Abhay Mann, Sakshi Makkar, Jasmine Kaur, Riya Kaushal Shah, Harbir Kaur, Nikhil Thukral, Siddharth Pravin Agrawal, William H Frishman, Wilbert S Aronow.
      Chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes in hematologic malignancies but is frequently complicated by cardiovascular toxicity, most notably in the setting of cytokine release syndrome. While systemic inflammation, endothelial activation, and myocardial stress have been implicated, the mechanistic links between immune activation and cardiac injury remain incompletely understood. Exosomes and other extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication during immune responses, carrying bioactive cargo including cytokines, microRNAs, proteins, and lipids that can modulate cardiovascular function. In the context of CAR-T therapy, EVs derived from activated T-cells, tumor cells, and injured endothelium may amplify inflammatory signaling, promote endothelial dysfunction, and contribute directly to myocardial injury. Importantly, EVs are detectable in peripheral blood and exhibit dynamic changes in concentration and cargo during CAR-T-associated toxicities, positioning them as promising biomarkers for early detection, risk stratification, and prognostication of cardiac injury. This review synthesizes current evidence on the biogenesis, functional roles, and cardiovascular effects of exosomes and EVs in CAR-T therapy, highlighting their potential as mechanistic mediators and translational biomarkers. We also discuss existing knowledge gaps, technical challenges in EV characterization, and future directions for integrating EV-based diagnostics into cardio-oncology practice.
    Keywords:  biomarkers; cardio-oncology; cardiotoxicity; chimeric antigen receptor T-cell therapy; cytokine release syndrome; endothelial dysfunction; exosomes; extracellular vesicles
    DOI:  https://doi.org/10.1097/CRD.0000000000001246
  21. Nat Cancer. 2026 Apr 16.
    Advances in predicting T cell epitope recognition for cancer immunotherapy.
    David Gfeller, Julien Racle, Alexandre Harari, Giancarlo Croce.
      T cell recognition of malignant cells is central to cancer immunotherapy. This process is elicited by interactions between T cell receptors (TCRs) and antigenic peptides displayed on major histocompatibility complex molecules. Sequencing technologies enable characterization of genomic, transcriptomic and epigenetic alterations that can give rise to epitopes in cancer cells, alongside TCR repertoire profiling in T cells. An important challenge is to determine which peptides are recognized by T cells and which TCRs mediate this recognition. This Perspective highlights how technological and computational advances have improved epitope predictions, shed light on TCR-epitope recognition and could help leverage TCR repertoires for therapeutic innovations in cancer immunotherapy.
    DOI:  https://doi.org/10.1038/s43018-026-01144-z
  22. Clin Transl Sci. 2026 Apr;19(4): e70561
    Thailand's Emerging Role in the Cell and Gene Therapy Revolution: A Review of Progress and Potential.
    Vip Viprakasit, Warut Tulalamba, Thidarat Suksangpleng, Supachai Ekwattanakit.
      This Perspective examines Thailand's role in cell and gene therapy, focusing on regulatory development and early clinical experience. These therapies are used in Thailand for β-thalassemia, or blood cancer, together with the evolving ATMP regulatory framework and the ATMP Sandbox Project. Rather than cataloguing global indications, we analyze how selected advances intersect with Thailand's health system, highlighting opportunities and constraints for its role as a regional site for ATMP research, manufacturing, and access in Southeast Asia.
    Keywords:  advanced therapeutic medicinal products (ATMPs); gene addition; gene editing; gene therapy; sandbox project
    DOI:  https://doi.org/10.1111/cts.70561
  23. Urol Oncol. 2026 Apr 15. pii: S1078-1439(26)00103-1. [Epub ahead of print] 111092
    Novel immunotherapies for prostate cancer.
    George Mo, Vivek Narayan.
      Since the advent of the autologous dendritic cell-based vaccine, sipuleucel-T, in 2010, the clinical development of immunotherapeutic approaches in advanced prostate cancer has largely been lacking. Aside from the infrequent use of pembrolizumab immune checkpoint blockade in rare molecularly-selected patients, no further immune approaches have achieved regulatory approval. Numerous challenges exist that preclude successful clinical development, including an immunologically-excluded tumor immune microenvironment, off-target and/or inflammatory toxicities that narrow the therapeutic window, and limited durability of anti-tumor responses. Nevertheless, recent advances in drug design and cellular engineering have reinvigorated interest in novel immunotherapeutic approaches in prostate cancer. This review provides an overview of the current landscape of novel immunotherapy clinical development for prostate cancer, with a focus on chimeric antigen receptor (CAR) T cells, T cell engagers, monoclonal antibodies, and cancer vaccine approaches that have produced promising early phase clinical data.
    Keywords:  Cancer vaccines; Chimeric antigen receptor T cell therapy; Immunotherapy; Prostate cancer; T cell engagers
    DOI:  https://doi.org/10.1016/j.urolonc.2026.111092
  24. Indian Pediatr. 2026 Apr 13.
    Democratizing the Cure: Indigenous Innovations and the Future of Pediatric Cell and Gene Therapy in India.
    Prasad Iyer, Rajat Bhattacharyya, Gaurav Kharya.
      Cell and gene therapy (CGT) represents a paradigm shift in the treatment of diseases once regarded incurable. This is particularly true for pediatric cancers and inherited disorders which often have a monogenic basis. While the global landscape of CGT is rapidly evolving with numerous approved products, India faces unique challenges in adopting high-cost, complex therapies. This perspective offers a comprehensive overview of the current status of pediatric CGT in India, emphasizing the urgent need for affordable and indigenous alternatives. We examined the spectrum of conditions for which CGT shows potential for pediatric patients, analyzed significant research and clinical studies from India, and investigated the pipeline of new products and therapies approaching clinical trials. This analysis provides a roadmap for the future of this transformative field in India in light of emerging regulatory and ethical regulations.
    Keywords:  Biologics; Cell therapy; Gene therapy; Hemophilia; Sickle cell disease; Thalassemia
    DOI:  https://doi.org/10.1007/s13312-026-00333-4
  25. Front Immunol. 2026 ;17 1794535
    Case Report: Transverse myelitis following CAR-T cell therapy for post-transplant lymphoproliferative disorder.
    Nicolas Desbaillets, Ana Isabel Martín-Quesada, Arthur Mulvey, Marie Le Moine, Eleonora Ghisoni, Raphael Stadelmann, Angela Koutsokera, Eleftheria Kampouri, Vincent Dunet, Andreas F Hottinger, Petr Szturz, Caroline Arber, Lionel Trueb, Bernhard Gentner, Blanca Navarro-Rodrigo.
      We report a case of severe, irreversible transverse myelitis following CD19-directed CAR-T cell therapy (axicabtagene ciloleucel) for refractory post-transplant lymphoproliferative disorder (PTLD) in a young female lung-transplant recipient. This case illustrates an emerging neurotoxic complication of CAR-T cell therapy and highlights convergent risk factors including demographics, tumor type and CAR construct. We discuss current evidence of CAR-T-associated myelopathy, its proposed inflammatory and immune-trafficking mechanisms, and the potential contribution of interleukins and chemokines such as IL-1, IL-6, IL-18, CCL-2 and CXCL10 signaling to spinal cord injury. We further address diagnostic challenges, and review current management strategies such as corticosteroids, IL-1 blockade, and IL-6 neutralization. This report underscores the need for heightened vigilance, early imaging, and systematic reporting to improve prevention and treatment of this rare but severe CAR-T-related neurotoxicity.
    Keywords:  Chimeric Antigen Receptor T-cell Therapy (CAR-T cell therapy); Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS); Post-Transplant Lymphoproliferative Disease (PTLD); cytokines; transverse myelitis
    DOI:  https://doi.org/10.3389/fimmu.2026.1794535
  26. J Vis Exp. 2026 Mar 27.
    Isolation, Cultivation, and Transient Transfection of Primary Human T Cells to Generate Chimeric Antigen Receptor (CAR) T Cells.
    Elisabeth A Lehner, Sanna M Riedl, Florian Haberl, Nicolina Skvorc-Winkler, Antonia M S Müller, Charlotte U Zajc.
      To assess the efficacy and potency of chimeric antigen receptor (CAR) T cells, it is essential to isolate, activate, expand, characterize, and genetically engineer primary human T cells. Compared to common T cell lines, primary cells can provide a more realistic model system, since they are highly variable, capable of T cell-mediated killing, and able to differentiate. Here, we provide a step-by-step protocol for all essential steps for the cultivation of primary T cells, including their isolation from blood products, activation, in vitro expansion, and transient transfection. We describe differences in expansion kinetics and differentiation of primary T cells upon activation with two different reagents and provide an antibody panel for flow cytometric analysis of T cell phenotype and activation state. We offer detailed instructions for electroporation of human T cells with mRNA encoding a CAR and assessing CAR expression kinetics over time. This protocol provides recommendations on ideal timepoints for downstream potency and efficacy assays of CAR T cells and the influence of different amounts of mRNA on signal intensity. Given the transient nature of this method, it provides a rapid and easy-to-implement possibility to test and compare many CAR constructs in parallel.
    DOI:  https://doi.org/10.3791/70162
  27. Int J Pharm. 2026 Apr 11. pii: S0378-5173(26)00310-8. [Epub ahead of print]697 126862
    Synergizing immunity: lipid nanoparticle-mediated mRNA and gene delivery as a next-gen paradigm in cancer immunotherapy.
    Amrita Arup Roy, Naitik Jain, Rahul Pokale, Geethu Madhusoodanan, Anoushka Mukharya, Syeda Ayesha Farhana, Bola Sadashiva Satish Rao, Jayant S Goda, Srinivas Mutalik.
      Messenger RNA (mRNA)-based therapeutics have revolutionised cancer immunotherapy by enabling transient, non-integrating expression of tumour antigens, cytokines, and immunomodulators. However, the inherent instability and immunogenicity of mRNA necessitate efficient delivery platforms led by lipid nanoparticles (LNPs). This review comprehensively discusses the evolution, design, and application of LNPs for mRNA and gene delivery in cancer immunotherapy. We explore their physicochemical properties, mechanisms of cellular uptake, endosomal escape, and immunogenic potential, alongside surface engineering strategies for tumour targeting. Special emphasis is placed on recent advances in LNP-based mRNA vaccines, CAR-T cell engineering, bispecific antibody delivery, and combinatorial therapies. The article synthesizes insights from preclinical studies, clinical trials, and scalable manufacturing innovations, including microfluidics and tangential flow filtration. Furthermore, we address storage stability, immunotoxicity, and regulatory hurdles that shape clinical translation. Together, these insights underscore LNPs as a transformative vehicle for next-generation mRNA cancer immunotherapies and highlight future directions in overcoming delivery and immune landscape barriers.
    Keywords:  Antigen-presenting cells (APCs); Cancer immunotherapy; Endosomal escape; Gene delivery; Lipid nanoparticles (LNPs); mRNA-based vaccines
    DOI:  https://doi.org/10.1016/j.ijpharm.2026.126862
  28. Cancer Immunol Immunother. 2026 Apr 15. pii: 146. [Epub ahead of print]75(5):
    Immunotherapy for pediatric solid tumors: overcoming biological barriers through rational multimodal combinations.
    Mahsa Fatahichegeni, Mohammad Amin Ansarian, Mi Xiao, Wenjuan Gao, Ruiming Shi.
      Pediatric solid tumors remain among the most treatment-refractory childhood malignancies, defined by biological features that have largely resisted the immunotherapeutic advances transforming adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and profoundly immunosuppressive tumor microenvironments collectively undermine the T cell-dependent mechanisms on which most current immunotherapies depend. Yet the field is undergoing a meaningful shift. Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma, and next-generation antibody-drug conjugates and bispecific T cell engagers targeting GD2, B7-H3, and GPC2 are extending the reach of antibody-based approaches across pediatric histologies. CAR T cell therapies have demonstrated clinical feasibility against multiple targets, with advanced engineering strategies, including cytokine armoring, bispecific constructs, and locoregional delivery, beginning to address fundamental barriers such as poor tumor infiltration, limited persistence, and antigen escape. Immune checkpoint inhibitors, while largely ineffective as monotherapy in unselected populations, induce durable responses in molecularly defined subsets such as mismatch repair-deficient and hypermutated tumors. Emerging platforms, including oncolytic virotherapy, NK cell engagers, and neoantigen vaccines, offer rational strategies to convert immunologically cold tumors into treatment-responsive phenotypes. Together, these advances point toward a future of combination immunotherapy tailored to the distinct immune biology of childhood cancers.
    Keywords:  Antibody–drug conjugates; CAR T cell therapy; Immune checkpoint inhibitors; Immunotherapy; Neuroblastoma; Pediatric solid tumors; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s00262-026-04384-1
  29. Int J Pharm X. 2026 Jun;11 100526
    A decade of innovation in healthcare: Automation, bio-printing and digital twin technologies for personalized therapies.
    Donya Ghavami, Nicola Giulietti, Giuseppina Sandri, Hermes Giberti.
      Advanced therapy medicinal products (ATMPs) face a distinct manufacturing challenge: delivering patient-specific therapies with reproducible quality, acceptable cost, and GMP-compliant manufacturing control. This narrative review examines how, over the past decade, the manufacturing of these therapies has moved from operator-dependent, open workflows toward more automated, closed or functionally closed, and increasingly data-supported process architectures. Three converging technology streams are discussed: (i) closed and semi-closed automated platforms for GMP-compliant cell manufacturing, (ii) advanced bioprinting and 3D manufacturing systems for tissue-engineered products, and (iii) digital twin concepts and related data-driven strategies as emerging enabling layers for monitoring, traceability, and process support. Across these domains, the dominant engineering trend is a shift from standalone equipment toward integrated frameworks aimed at reducing operator dependence, improving reproducibility, and strengthening GMP readiness. Overall, the field is shifting from isolated tools to more coordinated, automation-oriented, and increasingly data-supported workflows.
    Keywords:  3D printer; ATMPs; Automation; Bioprinter; Data-driven; Digital twin; GMP
    DOI:  https://doi.org/10.1016/j.ijpx.2026.100526
  30. Blood. 2026 Apr 16. 147(16): 1785-1787
    Reviving CD2 signaling to boost CAR T-cell therapy.
    Martina Seiffert.
      
    DOI:  https://doi.org/10.1182/blood.2025032721
  31. Int J Technol Assess Health Care. 2026 Apr 16. 1-35
    Ontology-driven generation of parameters for health technology assessment models: A prompt engineering study.
    Evelio González-González, Iván Castilla Rodríguez, Joel Aday Dorta-Hernández.
      
    DOI:  https://doi.org/10.1017/S0266462326103754
  32. J Biopharm Stat. 2026 Apr 14. 1-24
    Bayesian quantitative decision-making framework in cell and gene therapy development for rare diseases.
    Rui Kang, Yusuke Yamaguchi, Cong Han.
      Developing drugs including cell and gene therapies for rare diseases presents unique challenges, primarily due to small patient populations and limited clinical data. In such settings, traditional quantitative decision-making (QDM) frameworks, which play a crucial role in guiding go/no-go decisions in proof-of-concept (PoC) studies, often lead to inconclusive decisions due to limited information. This paper is the first study presenting a Bayesian QDM framework specifically tailored to cell and gene therapy candidates in the rare disease space, with an emphasis on borrowing information from external data sources to improve the robustness of QDM. While technical components of Bayesian QDM framework have been established in the literature, our contribution lies in (1) a unified framework accommodating both controlled and uncontrolled PoC studies with hypothetical controls, (2) the systematic integration of power priors with flexible control of information borrowing, and (3) practical implementation guidance through an open-source R Shiny application. The proposed framework offers potential advantages, such as more informed decision-making based on reduced trial durations and improved resource allocation, which are critical for accelerating drug development in rare diseases. Simulation studies and a case study are conducted to illustrate the practical application of Bayesian QDM, demonstrating its benefits in early-stage clinical trials.
    Keywords:  Bayesian statistics; Quantitative decision-making; cell and gene therapy; proof-of-concept study
    DOI:  https://doi.org/10.1080/10543406.2026.2655410
  33. Int J Mol Sci. 2026 Mar 24. pii: 2930. [Epub ahead of print]27(7):
    Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.
    Sadam Abubakar, Latifat Abdulsalam, Lamin Fatty, Rimsha Kanwal, Muhammad Naeem, Irshad Ahmad.
      Cancer immunotherapy has recently become an essential approach for treating cancer, showing considerable promise as a substitute for surgery, radiation therapy, and conventional chemotherapy. It primarily aims to boost the host's natural defense system to combat cancer malignancies by utilizing components of immune checkpoint blockades (ICBs), mainly programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), along with elements of adoptive cellular therapies (ACTs) like Chimeric Antigen Receptor (CAR) therapy, T Cell Receptor (TCR) therapy and Tumor-Infiltrating Lymphocyte (TIL) therapy. However, cancer cells tend to undermine the effectiveness of cancer immunotherapeutic strategies by employing one or more immune evasion mechanisms. This review briefly highlights how key mechanisms of cancer immune evasion confer resistance to immunotherapy and how the Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR)/Cas9 systems, as gene-editing tools, are poised to enhance cancer immunotherapy for treating challenging cancers. We emphasize that (CRISPR/Cas9) systems can be used to explore and positively alter the genes of the immune system, boosting the effectiveness of cancer immunotherapy by editing immune checkpoints, TILs, and CAR-T cells, and disrupting genes, facilitating tumors' evasion of the immune system. Furthermore, we highlight the growing interest in emerging base editor technology to engineer natural killer (NK) cells to overcome NK-cell-based immunotherapy challenges, particularly human leukocyte antigens (HLA)-mediated limitations, and to engineer CAR-T cells for improved immunotherapy outcomes.
    Keywords:  cancer immunotherapy; gene editing; immune evasion; tumor infiltration; tumor microenvironment (TME)
    DOI:  https://doi.org/10.3390/ijms27072930
  34. J Immunother Cancer. 2026 Apr 13. pii: e013878. [Epub ahead of print]14(4):
    Data-informed optimization of CAR T-cell therapy long-term follow-up.
    Betsy Foss-Campbell, Nancy Myers, Rakesh Awasthi, Dylan Bechtle, Mariette Boerstoel Streefland, Wendy Corbett, Benjamin Dewees, George Eastwood, Julie Jadlowsky, Lisa Joy Martin, Wendy Langeberg, Erin Lee, Amy Marshall, Gwen Nichols, Jamie Shapiro, Lana Shiu, Mark Stewart, Nicholas P Tschernia, Jennifer Willert, Hairong Xu, Carl H June.
      Following administration of chimeric antigen receptor (CAR) T-cell therapy, extensive long-term follow-up (LTFU) requirements and complex data collection processes have posed significant challenges for patients and providers. To reassess whether a 15-year LTFU period remains scientifically justified, we convened a multistakeholder working group that included representatives from patient advocacy groups, academia, industry, and government. This analysis incorporates newly aggregated primary data on composite percentages of adverse events (AEs) reported by year for five Food and Drug Administration-approved CAR T-cell therapies. Combined with previously published research, the findings indicate that AEs are infrequently reported after 3 years post-infusion, and secondary T-cell malignancy-the AE of primary concern based on the mechanism of action of CAR T-cell therapy-has predominantly been reported within the first 2 years. Based on current cumulative safety data, a 5-year follow-up period may be scientifically sufficient in both clinical trial and commercial settings. Additionally, we propose a streamlined process that leverages technological advancements to automate the transfer of focused safety data from electronic health records into a third-party database. To facilitate implementation, we recommend feasibility testing of this updated data collection approach using an established platform. We also outline regulatory policy considerations to most effectively enable adoption of these recommendations.
    Keywords:  Chimeric antigen receptor - CAR; Hematologic Malignancies; Secondary malignancy; Treatment related adverse event - trAE
    DOI:  https://doi.org/10.1136/jitc-2025-013878
  35. Int J Technol Assess Health Care. 2026 Apr 16. 1-8
    "Beyond Efficiency: Reimagining Health Technology Assessment in the Age of Artificial Intelligence".
    Manuel C Cossio, Ramiro Gilardino.
      
    DOI:  https://doi.org/10.1017/S0266462326103778
  36. Biochim Biophys Acta Rev Cancer. 2026 Apr 15. pii: S0304-419X(26)00064-8. [Epub ahead of print] 189592
    Emerging advantages of nano delivery systems in enhancing CAR-T/CRISPR-Cas9 mediated cancer therapeutics.
    Vikas Kumar Sahu, Purbasha Das, Subhasree Roy Choudhury, Surajit Karmakar.
      Viral vectors have long been central to cancer immunotherapy, particularly for ex vivo chimeric antigen receptor (CAR)-T cell engineering and cancer vaccine development. Despite their success, clinical translation remains limited by immunogenicity, insertional mutagenesis, restricted cargo capacity, and high production costs. These drawbacks not only compromise safety but also hinder scalability and repeated dosing, both of which are critical for durable cancer control. To overcome these barriers, non-viral nanocarrier systems have emerged as versatile and safer alternatives. Lipid nanoparticles, polymeric platforms, biomimetic exosome-like vesicles, and hydrogel-based systems enable targeted and controlled delivery of nucleic acids, immunomodulators, and chemotherapeutics with enhanced stability, reduced systemic toxicity, and improved biocompatibility. Beyond passive delivery, these smart nanocarriers can be engineered with tumor-targeting ligands, immune checkpoint modulators, or stimulus-responsive release mechanisms to reprogram the tumor microenvironment and potentiate T-cell and dendritic cell activation. Furthermore, the modularity of nanotechnology facilitates co-delivery of multiple therapeutic agents, including antigens, adjuvants, and checkpoint inhibitors, allowing synergistic immunotherapeutic outcomes. Recent advances in large-scale manufacturing and clinical translation of lipid nanoparticle-based mRNA vaccines underscore the feasibility of these systems for oncology applications. As cancer immunotherapy evolves toward personalization and combination regimens, nanobiotechnology offers a transformative platform to replace conventional viral vectors, advancing safer, more effective, and clinically scalable treatments.
    Keywords:  CAR-T; CRISPR-Cas9; Cancer immunotherapy; Nanoparticle; Non-viral delivery system
    DOI:  https://doi.org/10.1016/j.bbcan.2026.189592
  37. Front Genet. 2026 ;17 1819270
    Federated, governed, and interoperable? The emerging architecture of public human genomic data infrastructures: a European perspective.
    Marco Antonio Tangaro, Matteo Chiara, Graziano Pesole, Federico Zambelli.
      Public infrastructures for human genomic data are increasingly incorporating federated approaches alongside centralized and cloud-native models, yet operational federation remains constrained by unsolved challenges at the legal, semantic, and technical layers. We describe the current landscape along three analytical axes, taking a primarily European perspective while drawing on global examples to highlight broader trends. First, we compare architectural models, centralized archives such as the European Genome-phenome Archive (EGA) and the database of Genotypes and Phenotypes (dbGaP), cloud-native platforms for data analysis, and federated networks exemplified by the European Genomic Data Infrastructure (GDI), highlighting their specific trade-offs on scalability, sovereignty, and analytical flexibility. Second, we examine the governance layer, from the tension between the GDPR's consent requirements and large-scale secondary use, through the European Health Data Space (EHDS) and Health Data Access Bodies, to machine-readable authorization via GA4GH Passports and the Data Use Ontology. Third, we assess interoperability and semantic alignment, including the role of GA4GH technical standards, FAIR metadata principles, and emerging schema harmonization efforts such as the German Human Genome-Phenome Archive (GHGA). We argue that the central challenge is no longer building individual platforms, but aligning heterogeneous regulatory interpretations, metadata models, and trust frameworks across jurisdictions. Addressing this alignment gap will determine whether federated genomics delivers on its promise of large-scale, privacy-preserving data reuse.
    Keywords:  EHDs; GA4GH; GDPR; data governance; federated analysis; human genomic data; interoperability; trusted research environments
    DOI:  https://doi.org/10.3389/fgene.2026.1819270
  38. Recenti Prog Med. 2026 Apr;117(4): 193-196
    [The regional network for CAR-T therapies in the Lazio Region: a governance model for innovation and sustainability.]
    Valeria Belleudi, Michela Servadio, Silvia Alessio, Marco Finocchietti, Ilaria Cozzi, Paola Michelozzi, Marzia Mensurati, Antonio Addis.
      The CAR-T therapies are characterized by high clinical, organizational, and economic complexity, requiring the adoption of dedicated governance models capable of ensuring equitable access, appropriateness, and sustainability. In this context, the Lazio Region has developed a regional network for the management of CAR-T therapies based on a multidisciplinary steering committee, a network of hospital centers, an informative platform, and a system for planning needs and assessing appropriateness. The system is based on the Real-World Data and a Horizon Scanning approach for the continuous updating of therapeutic indications. This experience represents an example of sustainable and replicable governance for the management of advanced therapies at the regional level.
    DOI:  https://doi.org/10.1701/4674.46892
  39. BJC Rep. 2026 Apr 15. pii: 18. [Epub ahead of print]4(1):
    Precision oncology in the age of AI: lessons from AI-driven drug discovery and clinical translation.
    Wonbeak Yoo.
      Drug discovery has been constrained by extended timelines and high costs, as the cumulative requirements of preclinical validation, multi-phase clinical trials, and regulatory approval have been imposed. Recently, computational modeling has been explored as a supportive approach to accelerate the identification and refinement of therapeutic candidates. Proof-of-concept was provided in a phase 2a trial of a de novo-designed TNIK inhibitor in idiopathic pulmonary fibrosis, in which safety, tolerability, and pharmacodynamic target engagement were demonstrated, with a trend toward reduced functional decline. This study showed that AI-derived molecules can advance into human testing, but broader validation, mechanistic understanding, and regulatory alignment remain essential. In oncology, where tumor heterogeneity, clonal evolution, and therapeutic resistance continue to constrain durable clinical benefit, there is an increasing need for adaptive and data-informed drug discovery strategies. This Perspective reviews recent progress and limitations in AI-driven drug discovery and early clinical translation. It emphasizes how the clinical evaluation of an AI-generated TNIK inhibitor serves as an early translational reference and outlines practical strategies for integrating multi-omics data, federated model validation, and adaptive trial design to advance precision oncology-oriented therapeutics.
    DOI:  https://doi.org/10.1038/s44276-026-00221-1
  40. Drug Des Devel Ther. 2026 ;20 576169
    Therapeutic Alternatives to Recombinant Biologics: Mechanistic Framework, Clinical Evidence, and Selection Guidance.
    Sarfaraz K Niazi.
       Introduction: Recombinant biologics have transformed modern medicine but face persistent limitations, including high costs ($24,000-500,000 annually), injection burden, immunogenicity, manufacturing complexity ($200-500M in facility investments), and global barriers that limit access for billions worldwide. These challenges drive an urgent need for therapeutic alternatives.
    Areas Covered: We evaluate six primary alternative modalities across FDA- and EMA-approved agents and pipeline candidates (2014-2025): oral small molecules targeting intracellular pathways, RNA therapeutics using gene silencing, CD36-mediated protein degraders (PROTACs), pharmacological chaperones, substrate-reduction therapies, and oral peptide formulations []. Clinical evidence from multiple FDA approvals demonstrates successful substitution: fitusiran achieves an 84-91% reduction in bleeding, iptacopan provides 61% transfusion independence, and deucravacitinib achieves 58.7% PASI-75 response. We identify four mechanistic principles-pathway convergence targeting, functional mimicry, allosteric modulation, and tissue-selective approaches-that can guide recombinant drug substitutions. Manufacturing analysis reveals potential for substantial cost advantages, although actual patient access requires policy intervention beyond market forces.
    Expert Opinion: Therapeutic alternatives represent a fundamental evolution in pharmaceutical medicine, with molecular targets rather than modalities determining potential. Success requires a mechanistic understanding, precision patient selection using pharmacogenomics (CYP2D6, CD36 expression), and modality-specific monitoring. While mRNA-based protein replacement currently faces dosing control challenges that limit its suitability for chronic diseases, advances in self-amplifying mRNA and modRNA with controllable expression kinetics may address these limitations. The future landscape will feature complementary modality use optimized for clinical scenarios, with AI-driven discovery and personalized selection potentially improving response rates from 30% to 60% to over 80%. Global access requires technology transfer, regulatory harmonization, and value-based pricing to bridge the gap between manufacturing cost advantages and realized patient benefits.
    Keywords:  JAK inhibitors; RNA therapeutics; global drug access; pharmacological chaperones; precision pharmacotherapy; recombinant biologics; targeted protein degradation; therapeutic alternatives
    DOI:  https://doi.org/10.2147/DDDT.S576169
  41. Mol Psychiatry. 2026 Apr 14.
    Clinical innovations and future directions of nanoparticles in the treatment of psychiatric and neurological disorders.
    Ting-Ting Zhu, Pan-Miao Liu, Kenji Hashimoto, Jian-Jun Yang.
      Nanoparticles (NPs) provide a versatile toolkit for psychiatry and neurology by leveraging tunable size, surface chemistry, and payload control to overcome long-standing barriers in central nervous system (CNS) therapy. Lipid, polymeric, inorganic, and hybrid NPs can be engineered to traverse the blood-brain barrier (BBB) via receptor/transporter pathways, target specific cell types, and deliver sustained or stimuli-responsive release. Beyond drug delivery, NPs improve imaging, enable gene/RNA therapeutics, and support anti-inflammatory and neuroprotective strategies, advancing precision medicine. Preclinical studies in depression, schizophrenia, Alzheimer's disease, and Parkinson's disease show superior exposure, target engagement, and behavioral or cognitive benefits versus free drugs, including photothermal/photodynamic and nanobody-based approaches. Clinically, translation remains early: a handful of CNS-directed candidates (e.g., gold-based bioenergetic agents, intranasal lipid formulations, liposomal modulators) are in trials, while approvals largely lie outside CNS indications. Key hurdles include variable BBB integrity, immunogenicity and protein-corona effects, manufacturing and stability constraints, and limited effect-site exposure-response data in humans. This review outlines a translational playbook: model-informed development linking formulation to brain interstitial exposure; Quality-by-Design chemistry, manufacturing, and controls (CMC); stratified, adaptive trials with population PK/PD and harmonized biomarkers; and proactive safety monitoring with long-term registries. We also highlight NP strategies targeting the gut-brain axis-delivering probiotics, metabolites, or antimicrobials-as complementary routes to modulate neuroinflammation and circuit function. With rigorous clinical science, manufacturing quality, and safety governance embedded from the outset, nanotechnology is positioned to deliver safer, more effective, and potentially disease-modifying therapies for CNS disorders.
    DOI:  https://doi.org/10.1038/s41380-026-03603-6
  42. Digit Health. 2026 Jan-Dec;12:12 20552076261433141
    Streamlining regulation to Unlock Digital Health Innovation in the NHS.
    Yousef Yousef, Jacob Keast, Hajira Dambha-Miller.
      Digital health adoption in the National Health Service (NHS) remains fragmented despite significant technological advances and substantial government investment in innovation initiatives. Many promising digital solutions fail to progress beyond pilot phases, with implementation remaining inconsistent across trusts despite national strategies including the 2022 digital health and social care plan. This Viewpoint examines the principal obstacles to digital health commercialisation within the NHS, focusing on regulatory complexity, organisational fragmentation, limited financial capacity and cultural resistance to change. We review existing support mechanisms including the Digital Technology Assessment Criteria (DTAC), NHS Innovation Accelerator and Clinical Entrepreneur Programme, highlighting their strengths and persistent limitations. To accelerate adoption, we propose two key reforms: formalising DTAC as a mandatory national standard with subsidised compliance pathways for small and medium-sized enterprises, and establishing a national 'innovation passport' that harmonises DTAC, Medicines and Healthcare products Regulatory Agency and procurement requirements into a single, transferable assessment. These reforms, complemented by strengthened procurement coordination and cultural change initiatives, could create a more predictable pathway for digital innovation while maintaining rigorous patient safety standards and enabling equitable access to validated digital health tools across the NHS.
    Keywords:  DTAC; Digital health; NHS; SMEs; commercialisation; health policy; innovation adoption; regulation
    DOI:  https://doi.org/10.1177/20552076261433141
  43. Int J Mol Sci. 2026 Mar 30. pii: 3113. [Epub ahead of print]27(7):
    Viral Reactivation in Multiple Myeloma Patients Receiving Anti-BCMA Chimeric Antigen Receptor T-Cell Therapy.
    Ido Cohen, Eyal Lebel, Sigal Grisariu, Batia Avni, Shlomit Kfir-Erenfeld, Nathalie Asherie, Eran Zimran, Vladimir Vainstein, Miri Assayag, Tatyana Dubnikov Sharon, Rivka Alexander-Shani, Nomi Bessig, Alaa Shehadeh, Aseel Ishtay, Miriam Schlossberg, Marjorie Pick, Moshe E Gatt, Tali Bdolah-Abram, Polina Stepensky, Shlomo Elias.
      Chimeric antigen receptor T (CAR-T) cell therapy has become a standard of care for many hematological malignancies, and has significantly transformed treatment outcomes. However, CAR-T therapy is associated with specific toxicities, including infections. Although the anti-CD19 CAR-T risks are well-characterized, infectious complications following B-cell maturation antigen (BCMA)-directed CAR-T in multiple myeloma (MM) remain under-researched. In this study, we evaluated the incidence and clinical impact of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) reactivations in 75 patients receiving anti-BCMA CAR-T for MM, and compared them to 60 patients receiving commercial anti-CD19 CAR-T for B-cell lymphoma (BCL). The viral reactivation rates were 20% for CMV and 8% for EBV in the MM group, vs. 31.7% and 3%, respectively, in the BCL group. No ADV reactivations were seen in either cohort. Most of the CMV reactivations (87% in the MM cohort and 68.5% in the BCL cohort) were asymptomatic and clinically insignificant, and had no impact on progression-free survival (PFS) or overall mortality. Overall, these findings suggest that although CMV and EBV reactivations are relatively common after anti-BCMA CAR-T, they are rarely associated with meaningful disease, and the risks do not exceed those of CD19-directed therapy. Thus, routine pre-emptive screening for these viruses may be unwarranted in asymptomatic patients.
    Keywords:  B cell lymphoma; BCMA; CAR-T-cell therapy; Epstein–Barr virus; adenovirus; chimeric antigen receptor T cell; cytomegalovirus; multiple myeloma; viral reactivation
    DOI:  https://doi.org/10.3390/ijms27073113
  44. BMC Med Ethics. 2026 Apr 16.
    Determinants of willingness to share personal genomic data: a systematic review focused on health literacy.
    Marleen Schmeiss, Renate Schramek.
       BACKGROUND: Genomic medicine increasingly depends on patients' willingness to share genomic and medical data. While data sharing supports advances in personalised care, it also raises ethical and social concerns related to privacy, trust and participation. Understanding these factors requires attention to patients' health literacy and their capacity to interpret and act upon genomic information.
    METHODS: A systematic review was conducted according to PRISMA guidelines to identify empirical studies published between 2015 and 2025 that explored patients' understanding of genomic information and their willingness to share data. Searches were performed in PubMed, Web of Science and Scopus. Eligible studies included qualitative, quantitative and mixed-methods designs. Findings were synthesised thematically and Nutbeam's model of health literacy was used in the discussion to interpret the results.
    RESULTS: Fifteen studies met the inclusion criteria. Participants demonstrated basic understanding of genetic terms but limited knowledge of data infrastructures and governance. Trust was a central factor influencing willingness to share data, often compensating for limited genomic literacy. Moral and altruistic motives encouraged engagement, whereas financial considerations played a minor, context-dependent role.
    CONCLUSIONS: Data sharing in genomic medicine relies on more than factual knowledge. Strengthening health literacy through transparent, dialogue-based, and participatory approaches can promote informed, autonomous, and ethically responsible participation in genomic research.
    Keywords:  Data Governance; Genomic Data Sharing; Health Literacy; Patient Perspectives
    DOI:  https://doi.org/10.1186/s12910-026-01456-w
  45. Glob Reg Health Technol Assess. 2026 Jan-Dec;13:13 79-86
    Italian Medicines Agency's reform and time until pricing and reimbursement decisions: a time-to-event analysis.
    Gian Marco Raspolini, Bruno Federico, Mario Cesare Nurchis, Gianfranco Damiani, Raffaella Cocciolo, Paola Turella, Daniela Pilunni, Pierluigi Navarra.
       Introduction: The duration of pricing and reimbursement (P&R) negotiations is a key performance indicator for medicines agencies in universal health coverage systems. In early 2024, the Italian Medicines Agency (AIFA) underwent a major reform, including the merging of the previous Scientific-Technical Committee and Price and Reimbursement Committee into a single Scientific and Economic Committee. This study evaluates the reform's impact on time to P&R determinations for new medicines in Italy.
    Methods: A time-to-event analysis was conducted on 139 new chemical entities authorized by the European Commission (EC) between February 2021 and December 2023. The primary outcome was the time from marketing authorization (MA) to publication of AIFA's P&R determination. Kaplan-Meier curves and Cox proportional hazards models were used to compare reclassification hazards between pre- (before March 2024) and post-reform groups of medicinal products, based on a fixed separation date, adjusting for antineoplastic therapeutic area and pharmaceutical company size. Four sensitivity analyses tested the robustness of the results.
    Results: The multivariate Cox model, adjusting for antineoplastics, products from major corporations, and orphan medicines, showed that the reform was associated with an 84% increase in reclassification hazards (HR = 1.84, 95% CI 1.20-2.82, p = 0.005). Sensitivity analyses corroborated these findings, showing even greater improvements when focusing on national evaluation timeframes (HR = 11.57 and HR = 3.91).
    Conclusion: The consolidation of separate committees into a unified structure, as a part of the 2024 AIFA reform, was accompanied by accelerated P&R negotiations for new medicines in Italy, demonstrating that structural optimization of health technology assessment processes may enhance system efficiency.
    Keywords:  AIFA; Health Services Accessibility; Pharmaceutical policy; Pharmaceutical preparations; Pricing and reimbursement; Survival Analysis
    DOI:  https://doi.org/10.33393/grhta.2026.3671
  46. Rev Med Interne. 2026 Apr 16. pii: S0248-8663(26)00527-8. [Epub ahead of print]
    [Bispecific T-cell engagers for the treatment of autoimmune diseases: Current status and therapeutic perspectives].
    Marion Larue, Benoît Ferment, Vincent Allain, Jehane Fadlallah, Baptiste Hervier, Bertrand Arnulf, Alexis Talbot.
      Bispecific T-cell engagers (BiTEs) represent a new generation of immunotherapies capable of redirecting T lymphocytes toward specific targets, particularly B cells and their plasmacytic derivatives. Initially developed in hematology for the treatment of malignant hematologic disorders, BiTEs are now attracting increasing interest in the field of severe or refractory autoimmune diseases. Their mechanism of action relies on the formation of an immunological synapse between cytotoxic T cells and B cells and/or plasma cells expressing antigens such as CD19, CD20, or BCMA, thereby reducing autoantibody production through depletion of B cells and their plasmacytic derivatives. Unlike cellular therapies, this strategy does not require genetic modification or patient-specific manufacturing, offering potential advantages in terms of depth and durability of response, while also raising questions regarding safety, feasibility, and cost. This article provides an overview of preclinical and clinical data on the use of BiTEs in autoimmune diseases and discusses the perspectives and challenges associated with their development in this therapeutic area.
    Keywords:  Anticorps bispécifiques; Autoimmune diseases; B cells; Bispecific antibodies; Lymphocytes B; Lymphocytes T; Maladies auto-immunes; T cells; Targeted therapies; Thérapies ciblées
    DOI:  https://doi.org/10.1016/j.revmed.2026.03.441
  47. Soc Sci Med. 2026 Apr 08. pii: S0277-9536(26)00346-1. [Epub ahead of print]400 119270
    Governing the rise of AI in healthcare: A comparative governance document and implementation implications across five jurisdictions.
    Jinsong Chen, Mingli Pang, Wenrong Qian, Weifang Zhang, Caiming Xu, Ping He.
       BACKGROUND: As AI increasingly reshapes healthcare delivery and innovation, global health systems face urgent imperatives to govern its development, deployment.
    OBJECTIVE: Drawing on 43 regulatory and strategic documents in five jurisdictions, the study systematically assessed convergences and divergences in national AI strategies, risk classification schemes, software-as-a-medical-device (SaMD) frameworks, ethical oversight, and cross-border data policies.
    METHODS: Policy and regulatory documents on AI in health (2017-2025) were collected from health authorities, regulatory agencies, and multilateral platforms. A structured 20-item framework covering six domains was applied to enable systematic cross-jurisdictional comparison of strategic vision, regulatory rigor, ethics, implementation support, global alignment, and medical device governance.
    RESULTS: Increasing convergence around core principles such as transparency, accountability, and human-centric AI, particularly through the influence of international norms. However, significant divergence remained in regulatory maturity, enforcement mechanisms, reimbursement pathways and implementation capabilities. While jurisdictions like Singapore and China exhibited centralized, state-led coordination, others like the US reflected pluralistic, agency-driven models. Economic incentives, workforce readiness programs, and post-market surveillance systems also varied widely.
    CONCLUSION: The study concluded with five recommendations for advancing AI governance: strengthening interagency coordination, harmonizing regulatory frameworks, embedding equity and transparency in data infrastructure, supporting institutional readiness and fostering international collaboration.
    Keywords:  AI; Health policy; Health systems; Healthcare
    DOI:  https://doi.org/10.1016/j.socscimed.2026.119270
  48. Front Med (Lausanne). 2026 ;13 1768365
    Virus-directed CAR immunotherapies for chronic HBV and HIV: a systematic synthesis of preclinical and early clinical evidences.
    Sirwan Sleman, Masood B Ameen, Omed I Abid, Barham J Abdullah, Zaniar A Abass.
       Background: Chronic hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are among the most important global health issues. Virus-directed CAR-T and CAR-NK are promising strategies capable of targeting virally infected cells. The therapeutic potential, safety, and translational readiness of these platforms have not been fully synthesised.
    Objectives: This study assessed preclinical and early clinical evidence of CAR-T and CAR-NK immunotherapies against HBV and HIV, including efficacy, safety and translational feasibility.
    Methods: Databases were searched according to PRISMA 2020 guidelines. For this review, eligible studies included in vitro, in vivo, and clinical studies examining virus-directed CAR lymphocytes. Random-effects models generated pooled standardised mean differences (SMD) and risk ratios (RR). The level of specific evidence was considered by GRADE.
    Results: Forty-three studies met the inclusion criteria (21 in vitro, 14 in vivo, and 8 clinical). Preclinical HIV CAR-T models demonstrated significant reductions in HIV p24 antigen levels (pooled SMD = -1.15, 95% CI -1.50 to -0.80). Similarly, HBV-directed engineered T-cell studies showed a marked decrease in HBsAg and HBV DNA (SMD = -1.30, 95% CI -1.70 to -0.90). CAR-NK platforms displayed comparable antiviral activity with potentially improved safety profiles. In vivo analyses also indicated consistent suppression of HIV RNA (SMD = -0.92, 95% CI -1.26 to -0.58) and moderate reductions in HBV DNA levels (SMD = -1.05, 95% CI -1.52 to -0.63). In early-phase clinical studies (phase I/II), HIV-directed CAR-T therapies produced modest decreases in circulating HIV RNA (SMD = -0.35, 95% CI -0.60 to -0.12), while HBV-targeted therapies demonstrated small but detectable antiviral responses (SMD = -0.42, 95% CI -0.78 to -0.11). Across clinical cohorts, the incidence of cytokine release syndrome (CRS) remained low, occurring in fewer than 10% of treated patients.
    Conclusion: Virus-directed CAR-T and CAR-NK therapies show strong preclinical antiviral activity and early clinical signs of activity, showing acceptable safety. Because of heterogeneity, small sample size and limited clinical data, the quality of evidence from this population remains low to moderate. Large and well-controlled trials are necessary to optimise CAR designs, improve persistence, and investigate combinations with latency-reversing or immune-modulating drugs.
    Keywords:  CAR immunotherapies; chronic HBV; chronic HIV; immunotherapy; virus-associated CAR therapies
    DOI:  https://doi.org/10.3389/fmed.2026.1768365
  49. Med. 2026 Apr 10. pii: S2666-6340(26)00070-X. [Epub ahead of print]7(4): 101067
    Disruptive innovation in breast cancer therapeutic development.
    Sridatta V Teerdhala, Hannah L Chang, Isaac S Chan.
      Therapeutic development by nature is disruptive. By applying Christensen's disruptive innovation framework, we analyze why mutation-anchored agents somtimes underperform, why broadly acting therapies succeed as disruptive therapies, and how host-driven, subtype-agnostic modalities, such as immunotherapy, antibody-drug conjugates, and cell and gene therapies, offer a blueprint for scalable and durable clinical and commercial impact.
    DOI:  https://doi.org/10.1016/j.medj.2026.101067
  50. Cancer Innov. 2026 Apr;5(2): e70053
    Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.
    Rangzi Yi, Zijian Zhang, Yang Yang, Haichuan Zhu.
      Chimeric antigen receptor (CAR) T-cell therapy has been proved to be an effective cancer immunotherapy strategy against haematological malignancies, but exhaustion, limited persistence, and treatment-related toxicity have been identified as major roadblocks in solid tumour treatment. Small-molecular compounds could effectively improve CAR T-cell therapy, such as preventing exhaustion, enhancing memory formation, and enhancing the antitumor activity. Additionally, adding small molecule switches based on tetracycline-controlled gene expression system is an effective strategy to improve the safety of CAR T therapy and reduce its side effects. Despite the encouraging preclinical and clinical results, challenges still remain in optimizing dosing regimens and managing drug interactions. This review aims to summarize recent advances in combined approach and to discuss the underlying mechanisms of its potential benefits.
    Keywords:  CAR T; T‐cell exhaustion; combined therapy; immunotherapy; molecular compound
    DOI:  https://doi.org/10.1002/cai2.70053
  51. Crit Rev Oncol Hematol. 2026 Apr 10. pii: S1040-8428(26)00220-9. [Epub ahead of print]223 105333
    Cytokine-based NK cell engineering for cancer immunotherapy.
    Qiao Tang, Zhigang Tian, Jiacheng Bi.
      Natural killer (NK) cells are critical effector cells of the innate immune system and play essential roles in antiviral defense and antitumor immunity. In recent years, they have emerged as a major focus in the field of cancer immunotherapy. Cytokines constitute the fundamental molecular basis for regulating NK cell development, survival, proliferation, and effector functions, and also serve as key modulatory tools in NK cell engineering. This review summarizes recent progress in cytokine-driven NK cell engineering strategies and their applications in immunotherapy. It outlines the key cytokines associated with NK cell biology and the signaling pathways through which they regulate NK cell proliferation, activation, cytotoxicity, cytokine secretion, and the induction of cytokine-induced memory-like (CIML) NK cells. It further examines cytokine-based engineering strategies, with particular emphasis on IL-15-mediated support of NK cell expansion, functional maintenance, and persistence, including cytokine-supported culture systems, secreted IL-15, membrane-bound IL-15 (mbIL-15), and IL-15/IL-15Rα fusion formats. Future advances in precise signal modulation, controllable expression systems, and multi-cytokine synergistic strategies may help optimize therapeutic efficacy and facilitate the transition of NK cell therapy from empirical expansion approaches toward programmable signaling design.
    Keywords:  Adoptive NK transfer; Antitumor immunity; Cytokine engineering; Cytokines; NK cell immunotherapy
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105333
  52. Oncologist. 2026 Apr 08. pii: oyag129. [Epub ahead of print]
    Landscape of T-Cell Engagers in Solid Tumors.
    Esther Garcia-Lorenzo, Miriam Dorta, Bernard Doger, Manuel Pedregal, Victor Moreno.
      T-cell engagers (TCEs) are a diverse class of bispecific and multispecific molecules that co-bind CD3 on T cells and tumor-associated antigens to form an immune synapse and induce targeted T-cell-mediated cytotoxicity. While TCEs have demonstrated remarkable efficacy in hematologic malignancies, translation into solid tumors has been more challenging. Recent advances seen with tebentafusp in metastatic uveal melanoma and tarlatamab in small-cell lung cancer have validated the approach and driven a rapidly expanding pipeline targeting other tumor associated antigens such as STEAP1, MUC16, and PRAME among others. Unique challenges in solid tumors include antigen heterogeneity and density thresholds, on-target/off-tumor toxicities, and physical and immunologic barriers within the tumor microenvironment. To address these, next-generation engineering strategies, such as half-life extension, protease- or context-dependent masking, multispecificity, and "armed" constructs incorporating cytokine or co-stimulatory payloads, are being developed to enhance intratumoral activity while limiting systemic toxicities. Combination regimens with checkpoint blockade, chemotherapy, targeted therapies, and oncolytic platforms are also being actively investigated to overcome immune resistance and improve durability of response. Collectively, next-generation TCEs guided by rational target selection, context-dependent activation, and biomarker-driven patient stratification, are poised to broaden the reach of immunotherapy in solid tumors. In this review, we synthesize the recent advances that aim to expand the therapeutic window of TCEs for the treatment of solid tumors.
    Keywords:  T-cell engagers; bispecific antibodies; cytokine release syndrome; immunotherapy; solid tumors
    DOI:  https://doi.org/10.1093/oncolo/oyag129
  53. Front Drug Deliv. 2026 ;6 1793322
    Nanoparticle-mediated mRNA delivery for cancer, autoimmunity, and genetic diseases: a rapid review.
    Okechukwu Paul-Chima Ugwu, Fabian C Ogenyi, Mariam Basajja, Chinyere N Ugwu, Mundu M Mustafa, Michael Ben Okon.
       Introduction: Messenger RNA (mRNA) therapeutics have advanced from experimental platforms to clinical application, driven largely by the success of lipid nanoparticle (LNP)-based COVID-19 vaccines. Building on this progress, nanoparticle-mediated mRNA delivery is being extended to non-infectious indications, including oncology, autoimmune disorders, and inherited diseases. However, challenges such as extrahepatic targeting, endosomal escape, repeat-dose immunogenicity, thermostability, and scalable manufacturing remain significant barriers to translation.
    Methods: A rapid review of peer-reviewed studies and registered clinical trials published between January 2020 and October 2025 was conducted. Searches were performed in PubMed, Scopus, Web of Science Core Collection, and ClinicalTrials.gov using combined terms related to RNA modality and nanoparticle delivery. Eligible studies focused on non-viral nanoparticle platforms for therapeutic, non-infectious mRNA delivery, including applications in protein replacement, genome editing, and immune modulation. Screening yielded 15 studies for inclusion.
    Results: LNPs remain the most clinically advanced platform for therapeutic mRNA delivery. At the same time, polymeric, peptide-based, exosome-inspired, and hybrid nanoparticle systems are expanding the delivery landscape. Emerging RNA formats, including self-amplifying RNA and circular RNA, show potential to prolong expression at lower doses. Clinically, individualized mRNA neoantigen therapy (mRNA-4157/V940) combined with pembrolizumab reduced recurrence risk by approximately 49% in high-risk melanoma in the KEYNOTE-942 phase 2b trial, supporting phase 3 development. In cystic fibrosis, inhaled CFTR mRNA (ARCT-032) advanced to phase 2 after early phase 1 data demonstrated safety and tolerability.
    Discussion: Evidence for non-viral nanoparticle-mediated mRNA therapeutics is strong in preclinical research and increasingly promising in clinical applications beyond vaccinology. While LNPs dominate current translation, alternative carriers and improved RNA formats may broaden tissue targeting and therapeutic durability. Advances in biodegradable ionisable lipids, organ-selective LNPs, and lyophilised or solid formulations are being developed to address persistent delivery and manufacturing constraints. As the field matures, regulatory and policy frameworks will need to align with therapeutic endpoints and support long-term safety monitoring.
    Keywords:  autoimmunity; cancer immunotherapy; circular RNA; genetic therapy; lipid nanoparticles; messenger RNA; non-viral delivery
    DOI:  https://doi.org/10.3389/fddev.2026.1793322
  54. Transfusion. 2026 Apr 14.
    The status of cell and gene therapy education in medical schools-An international survey.
    Edina A Wappler-Guzzetta, Alexandra M Tabacu, Elena Nedelcu.
       INTRODUCTION: Cell and gene therapy (CGT) has emerged as a distinct medical field with more than 50 "Food and Drug Administration (FDA)"-approved products treating conditions from leukemia to sickle cell disease. Despite this therapeutic revolution and the field's inherent complexity, the status of CGT education in medical schools remains unknown.
    STUDY DESIGNS AND METHODS: This study explores the current state of CGT education in medical school curricula internationally and evaluates educators' perspectives on training adequacy and curriculum development needs. An international survey of 504 medical schools across six continents was conducted between September 2023 and April 2024. The 20-question poll assessed institutional characteristics, CGT educational requirements and structure, faculty resources, curriculum content, and educator perspectives. Descriptive statistics were calculated for all responses.
    RESULTS: Forty-six medical schools from 21 countries responded (9.1% response rate). Only 41% (19/46) offered CGT education, predominantly as optional courses (53%) during third and fourth years. Most programs relied on 2-4 faculty with competing responsibilities; only two institutions had dedicated CGT educators. Three schools reported standardized curricula, and none formally assessed student learning. Most educators (56%) considered current CGT education inadequate, and 78% advocated expansion. Nearly two-thirds (64%) agreed to integrate professionally developed online CGT courses.
    CONCLUSION: Medical education lags substantially behind the clinical adoption of CGT. The gap threatens future physicians' ability to offer optimal care. Strong educator consensus on inadequacy and interest in standardized resources signals an opportunity for intervention through collaborative curriculum initiatives.
    Keywords:  cell and gene therapy; educational gap; global survey; medical education
    DOI:  https://doi.org/10.1111/trf.70226
  55. NPJ Digit Med. 2026 Apr 15.
    Advancing FDA New Approach Methodologies from animal models through digital twins.
    Ashley L Eadie, Holly Fernandez Lynch, Naomi Scheinerman, Ravi B Parikh.
      In April 2025, the U.S. Food and Drug Administration announced immediate steps toward replacing animal testing for drug evaluation with New Approach Methodologies (NAMs)-modern laboratory techniques mimicking human tissues. However, significant gaps exist between current regulatory frameworks and these technologies' promise. We argue that specific comprehensive regulatory reforms will improve transition to human-relevant drug-evaluation methodologies, laying groundwork for digital twins, in silico trials, and transformative advances in precision medicine.
    DOI:  https://doi.org/10.1038/s41746-026-02476-x
  56. Extracell Vesicles Circ Nucl Acids. 2026 ;7(1): 292-301
    The regulatory landscape for extracellular vesicle therapies: Australian context and future directions.
    Christopher Rudge, Reeve McClelland, Wojciech Chrzanowski, Ryan L Davis.
      Extracellular vesicles (EVs) are emerging as promising tools for regenerative medicine and drug delivery, offering unique therapeutic advantages. However, their clinical translation - in Australia and globally - faces persistent challenges. These are commonly framed as technical issues stemming from inherent EV variability and the absence of standardized potency assays. While no EV-based therapeutic has yet received full market approval from any major regulatory agency, this Perspective argues that the barriers to translation are not solely technical but reflect limitations within current regulatory frameworks. In Australia, the Therapeutic Goods Administration (TGA) requires biological products to be included on the Australian Register of Therapeutic Goods (ARTG) before supply to market. However, several alternative regulatory pathways exist that can facilitate clinical access to "unapproved" products. Through analysis of these pathways, and comparison with international approaches, this Perspective highlights how regulatory inflexibility may be as significant a barrier to translating EV medicines as the technical difficulties themselves. Drawing on insights from governmental inquiries into the approval and subsidization of emerging medicines, the Perspective calls for reform of Australia's regulatory systems - including development of EV-specific guidance and policy that introduces adaptive assessment pathways - to better support the safe and timely integration of novel biotechnologies.
    Keywords:  Australian therapeutic goods regulation; Extracellular vesicles; innovative medicines regulation; precision medicine variability
    DOI:  https://doi.org/10.20517/evcna.2025.129
  57. Expert Opin Pharmacother. 2026 Apr 17. 1-9
    Phenotypic response surface-guided pharmacotherapy for personalized combination treatment in complex diseases.
    Atif Ali Khan Khalil, Muhammad Saeed Akhtar, Wajid Zaman, Adnan Amin, Sajid Ali.
       INTRODUCTION: Optimizing multidrug regimens for complex diseases remains a major challenge in precision medicine because responses are shaped by interpatient heterogeneity, nonlinear drug interactions, and incomplete mechanistic knowledge. Phenotypic Response Surfaces (PRS) have emerged as a promising computational and translational framework for guiding pharmacotherapy by linking phenotypic information with the rational optimization of combination treatments.
    AREAS COVERED: This review synthesizes literature identified through PubMed, Web of Science, and related biomedical databases, emphasizing PRS platforms, artificial intelligence-enabled phenotypic optimization, and personalized combination pharmacotherapy. Evidence from oncology, infectious diseases, transplantation medicine, and autoimmune disorders is examined to show how PRS-guided approaches can identify effective drug combinations and dose configurations, particularly where experimental, mechanistic, or clinical data are limited. The review also evaluates translational developments, clinical investigations, and emerging advances that may accelerate clinical implementation of PRS-guided treatment design.
    EXPERT OPINION: PRS-guided pharmacotherapy represents a transformative strategy for personalized combination treatment in complex diseases by integrating phenotypic response data with computational optimization to improve therapeutic precision. However, broader clinical adoption will require rigorous external validation, integration of multimodal patient data, improved interpretability of AI-assisted models, and supportive regulatory frameworks. With these advances, PRS-based approaches may become an important component of next-generation precision pharmacotherapy.
    Keywords:  PRS-guided treatment; Precision medicine; combination therapy; dosing optimization; personalized medicine; phenotypic response surfaces
    DOI:  https://doi.org/10.1080/14656566.2026.2660981
  58. Int J Health Policy Manag. 2026 ;pii: 9383. [Epub ahead of print]15 9383
    Advancing Public Health Through Internationally Coordinated Medical Device Registries Comment on "Quality and Utility of European Cardiovascular and Orthopaedic Registries for the Regulatory Evaluation of Medical Device Safety and Performance Across the Implant Lifecycle: A Systematic Review".
    Herbert Mauch.
      This commentary draws on findings from Hoogervorst et al1 to underscore the urgent need for internationally coordinated medical device registries, addressing the fragmentation and inconsistency currently limiting their utility in Europe. It advocates for registries governed by academic specialty societies to ensure scientific integrity, transparency, and clinical relevance. Such registries can significantly enhance post-market surveillance, support regulatory compliance and accelerate real-world evidence (RWE) generation. The importance of standardized data collection, regular outcome reporting, and contributor recognition to foster engagement and improve data quality is highlighted. By complementing randomized controlled trials (RCTs), registries can detect rare adverse events, inform clinical guidelines and drive innovation. Actionable recommendations for governance, data harmonization and interoperability are given, emphasizing that now is the time for academic societies to lead this transformation for the benefit of patients and healthcare systems globally.
    Keywords:  Academic Societies; International Coordination; Medical Device Registries; Post-Market Surveillance; Real-World Evidence (RWE)
    DOI:  https://doi.org/10.34172/ijhpm.9383
  59. Front Immunol. 2026 ;17 1740360
    Familial and genetic overlap between Sjögren's disease and other autoimmune diseases.
    Hitomi Ono-Minagi, Takuma Ohnishi, Natalie Atyeo, Kentaro Okuno, Peter D Burbelo, John A Chiorini.
       Purpose: To evaluate familial clustering of Sjögren's disease (SjD) with other autoimmune diseases and to characterize shared genetic architecture using an integrative genomic approach.
    Methods: Meta-analysis identified studies assessing autoimmune disease incidence in probands and first-degree relatives (FDRs), and pooled relative risks (RRs) were calculated. Publicly available genome-wide association study (GWAS) summary statistics were analyzed within a hierarchical genetic architecture framework integrating genome-wide polygenic correlation (LDSC), locus-level overlap (Jaccard index), union-based susceptibility mapping, and SNP-level pleiotropy detection.
    Results: Eighteen studies evaluated familial aggregation of SjD and other autoimmune diseases, of which nine were included in the pooled analysis. The RR of SjD was 10.54 when both proband and FDR were affected. Among discordant autoimmune probands, systemic lupus erythematosus (SLE) showed the highest RR for SjD (4.49), followed by systemic sclerosis (2.65). Genome-wide analyses demonstrated substantial polygenic sharing between SjD and systemic autoimmune diseases, positioning SjD as a bridging disorder. However, locus-level overlap was largely driven by the HLA region; after HLA exclusion, shared loci markedly decreased and were restricted to a limited number of immune regulatory hubs. SNP-level pleiotropy analyses similarly indicated predominantly HLA-dependent sharing with fewer non-HLA signals.
    Conclusion: SjD shows strong familial aggregation and shared genetic susceptibility with multiple autoimmune diseases. These findings support a hierarchical model in which broad HLA-driven polygenic sharing coexists with selective non-HLA convergence.
    Strengths and limitations of this study: This study integrates systematic familial meta-analysis with GWAS data to characterize shared autoimmune genetic architecture. However, inference regarding shared causal variants remains limited by reliance on summary statistics and locus-based resolution.
    Keywords:  Sjögren’s syndrome; autoimmune disease; familial risk; gene variant; genetic predisposition; risk factors
    DOI:  https://doi.org/10.3389/fimmu.2026.1740360
  60. Pharmacoecon Open. 2026 Apr 12.
    Trial-Based Economic Evaluations Conducted alongside Studies Embedded in Australian Healthcare Services and Programs: A Scoping Review.
    Belinda Wang, Catherine Sherrington, Luiza R Pivotto, Stanley Saputra, Josielli Comachio, Joanne Scarfe, Zoe Szewczyk, Nathalia Costa, Alison Pearce, Leanne Hassett, Andrew Milat, Christopher Williams, Wing S Kwok, Justin Yu, Kirsten Howard, Marina B Pinheiro.
       OBJECTIVES: The objective of this study was to map the literature and provide an overview of economic evaluations (EEs) conducted alongside studies embedded in Australian healthcare services or programs by: (1) providing a broad overview of the volume, characteristics and types of EEs and (2) examining the subset of EEs impacting older Australians in greater depth including characteristics (type, costs, outcomes, perspectives adopted, time horizon) and quality.
    METHODS: We conducted a scoping review of full trial-based EEs of studies embedded in Australian healthcare services and programs, published in peer-reviewed journal publications. Medline, Informit, ProQuest Central, Web of Science, Econlit, PsychINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cost-Effectiveness Analysis (CEA) Registry, and the International Health Technology Assessment (HTA) database were searched from inception to May 2025. Quality assessment was conducted using the Consensus Health Economic Criteria (CHEC-list).
    RESULTS: We identified 88 articles (86 studies) reporting 107 EEs. Cost-effectiveness analyses (CEA) were most common (n = 53, 50%). Most interventions were delivered in ambulatory care settings (n = 41, 47%) and included participants from metropolitan areas (n = 81, 92%). A total of 28 studies (29 comparisons) were with older adults, reporting 38 EEs. Among these, CEAs (n = 16, 42%) and adoption of a health system perspective (n = 11, 29%) were most frequent. Most EEs included intervention costs (n = 25, 86%) and healthcare costs (n = 28, 97%). Most interventions evaluated in CEA and cost-utility analysis were found to be more costly and more effective (n = 16, 43%) or less costly and more effective (n = 15, 41%). The median CHEC-list was 16/19 (IQR 13-17).
    CONCLUSIONS: Our review identified a diverse range of intervention types and evaluation methods, but a relative lack of cost-benefit analyses, despite their value for cross-sector comparisons. Most evaluations were conducted in metropolitan settings and few incorporated broader costs such as aged care, particularly regarding interventions targeting older adults. Future research should prioritize evaluations that include rural and remote populations and adopt broader perspectives, ensuring the full value of interventions is captured to better inform policy and decision-making.
    DOI:  https://doi.org/10.1007/s41669-026-00652-z
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