bims-carter Biomed News
on CAR-T Therapies
Issue of 2026–03–22
43 papers selected by
Luca Bolliger, lxBio
  1. Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.
  2. Driving CAR therapies beyond T cells.
  3. Manufacturing CAR T Therapies: A Review of Methods, Controls, and Innovations for Scalable, Accessible Treatments.
  4. CAR T cell therapy for fighting IPF: perspectives on a living drug.
  5. Cellular therapies for rheumatic disease.
  6. Next-generation immune cell therapies for lung cancer: advances in CAR-T, NK, and TIL strategies.
  7. Rewiring immunity: CAR-T cells as a paradigm shift in hematologic oncology.
  8. Statistical Methods for CAR-T cell Therapy Outcomes: A Review and Practical Considerations.
  9. Memory programming and new manufacturing paradigms in CAR-T cell therapy.
  10. The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia.
  11. Regulatory and HTA framework for herbal medicines in Indonesia.
  12. Novel non-viral in vivo CAR-T therapies: latest updates from the 2025 ASH annual meeting.
  13. Progress and challenges in CAR-T cell therapy for bladder cancer.
  14. IL12-engineered human PSMA-CAR T cells for the treatment of advanced prostate cancer.
  15. Anti CD19 targeting CAR T cell therapy in ANCA-associated vasculitis.
  16. Automated manufacturing of clinical-grade BDCA2 CAR NK cells in a closed system for the treatment of blastic plasmacytoid dendritic cell neoplasm.
  17. Preclinical comparison of non-signaling domain in CD19 CAR T cell with interleukin-7 receptor alpha signaling domain.
  18. [In vivo CAR-Ts, a significant breakthrough].
  19. Safety and efficacy of JWATM204, a novel Glypican-3 (GPC3)-targeted CAR T cell therapy for advanced hepatocellular carcinoma: A phase I dose-escalation study.
  20. Cost-Effectiveness of Maintaining Higher Stem-Cell Collection Thresholds in the Chimeric Antigen Receptor T-Cell Era for Multiple Myeloma.
  21. China's Pharmaceutical Ascent: Opportunity for Global Health, Test for US Leadership.
  22. Second-Generation and Off-the-Shelf CAR Platforms: Emerging Cardiovascular Implications of Next-Generation Cellular Immunotherapies.
  23. The Significance of Model-Based Strategies in Drug Development throughout the Lifecycle and Regulatory Decision-Making.
  24. A targeting lentiviral vector for generation of CAR-T cells in vivo.
  25. One lineage, many diseases: γδ T cells as context-dependent immune surveyors.
  26. Progress of biological agents and CAR cell therapy in the treatment of common autoimmune diseases in children.
  27. Emapalumab in pediatric patients with high-grade cytokine release syndrome associated with CAR T-cell therapy.
  28. Immune checkpoint targeted drug conjugate therapies: Bridging preclinical and clinical innovation for solid tumor therapy.
  29. Artificial Intelligence as a Disruptive Force in Pharmaceutical Innovation: Transforming Discovery, Development, and Manufacturing.
  30. Engineering BiTE-inspired IPSC-exosomes to potentiate CAR-T cell therapy against lung cancer.
  31. mRNA-based CAR T cell engineering: Unmodified mRNA enables high CAR expression without innate immune activation in T cells.
  32. The role of gut microbiota in autoimmune disease progression and therapy: a comprehensive synthesis.
  33. The gut-tumor metabolic axis: A comprehensive exploration of bidirectional crosstalk in cancer immunotherapy.
  34. New rules spur cell and gene therapy trials in China.
  35. Expert participation in the health technology assessment process: a scoping review.
  36. What patients value in data reuse for oncology research: a multi-stakeholder qualitative study to inform the European Health Data Space implementation in Belgium and beyond.
  37. Are we there yet? The road to faster and more efficient CAR T cell manufacturing.
  38. T-cell receptor-engineered T cells (TCR-e T cells): A novel cellular therapy for hematopoietic malignancies?
  39. Digital Public Reporting Systems for Evaluating Health Care Quality: Systematic Review.
  40. CRISPR-Cas9: Genome Engineering and Future Vaccine Applications.
  41. Regulatory Approaches to Electronic Labelling in the USA, EU, and India: A Comparative Overview.
  42. Strategic Integration of Electronic Quality Management Systems with Quality Risk Management: Advancing Pharmaceutical Compliance and Operational Excellence.
  43. Successful Use of Chimeric Antigen Receptor T-cell (CAR-T) Therapy With Lisocabtagene Maraleucel in a Renal Transplant Recipient With Refractory/Relapsed Diffuse Large B-Cell Lymphoma (DLBCL).
  1. Precis Clin Med. 2026 Mar;9(1): pbag007
    Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.
    Xiaohong Liu, Hongye Gao, Jianhua Yu.
      Chimeric antigen receptor (CAR)-engineered immune cells have revolutionized cancer immunotherapy, expanding from the established success of CAR-T cells to a diverse array of cellular platforms. While seven Food and Drug Administration-approved CAR-T cell products demonstrate unprecedented efficacy in hematologic malignancies, significant limitations persist, including severe inflammatory toxicities, resistance in solid tumors, and manufacturing barriers. These challenges have catalyzed extensive research to extend CAR engineering into alternative effector cell types, such as unconventional T cell subsets, natural killer (NK) cells, macrophages, neutrophils, and dendritic cells, as well as non-immune platforms. Each cell type exhibits distinct antitumor mechanisms, persistence profiles, safety characteristics, and manufacturing requirements, positioning them to address complementary therapeutic needs. This review provides a comprehensive overview of diverse CAR-engineered cellular platforms, encompassing their biological properties, advantages, sourcing strategies, and manufacturing processes, alongside current clinical progress and optimization approaches. Beyond oncology, these platforms have demonstrated significant potential in treating autoimmune diseases, infections, cardiac fibrosis, and senescence-associated disorders. By leveraging distinct immune and non-immune cell types to mediate cytotoxicity or suppress pathogenic cells, CAR technology provides versatile therapeutic avenues across varied disease contexts. Through synthesis of recent advances in CAR platform diversity, this review identifies opportunities for targeted optimization and explores future directions for broadening CAR-based therapeutic applications.
    Keywords:  CAR-engineered cells; adoptive cell therapy; cancer treatment; chimeric antigen receptor; immunotherapy
    DOI:  https://doi.org/10.1093/pcmedi/pbag007
  2. Trends Cancer. 2026 Mar 18. pii: S2405-8033(26)00039-7. [Epub ahead of print]
    Driving CAR therapies beyond T cells.
    Cecilie Ø Madsen, Thomas M Hulen, Maria Ormhøj, Sine R Hadrup, Inge M Svane, Özcan Met.
      Chimeric antigen receptor (CAR)-T cell therapy has reshaped cancer immunotherapy for hematological malignancies, yet progress in solid tumors remains limited. Physical barriers, antigen heterogeneity, and immunosuppressive tumor microenvironment restrict the activity and persistence of CAR-T cells, while safety concerns complicate target selection. Extending CAR technology to alternative immune lineages, such as macrophages, natural killer cells, tumor-infiltrating lymphocytes, and unconventional T cells, offers complementary mechanisms for tumor recognition, infiltration, and immune modulation. This review highlights recent advances in these emerging CAR platforms, compares their biological and translational features, and outlines how integrating cell-intrinsic properties with CAR design may guide the next generation of cellular immunotherapies for solid tumors.
    Keywords:  CAR-T therapy; NK cells; macrophages; tumor-infiltrating lymphocytes; unconventional T cells
    DOI:  https://doi.org/10.1016/j.trecan.2026.02.008
  3. PDA J Pharm Sci Technol. 2026 Mar 17. pii: pdajpst.2025-000059.1. [Epub ahead of print]
    Manufacturing CAR T Therapies: A Review of Methods, Controls, and Innovations for Scalable, Accessible Treatments.
    Jose A Caraballo-Oramas.
      Chimeric antigen receptor (CAR) T cell therapies have transformed the treatment of hematologic malignancies, providing meaningful clinical outcomes for patients with limited therapeutic options. However, the complexity of these therapies presents significant manufacturing challenges that could affect cost, scalability, and accessibility. Early CAR T production relied on highly manual, variable processes developed in academic settings, while current commercial manufacturing has moved toward more structured and standardized platforms. This review examines how that transition unfolded, with particular attention to changes in process design, analytical control strategies, and quality systems that support more robust manufacturing operations. Rather than individual technologies, the literature emphasizes increased levels of maturity in process controls as the defining feature of progress in manufacturing. Improvements in unit operations have helped enable more predictable scale-out of therapies, reinforcing the role of manufacturing in translating scientific innovation into consistent clinical delivery.
    Keywords:  ATMP; Analytical control strategy; Car T cell therapy; Cell and Gene Therapy Manufacturing; GMP; automation; closed systems; process scalability
    DOI:  https://doi.org/10.5731/pdajpst.2025-000059.1
  4. Front Immunol. 2026 ;17 1770081
    CAR T cell therapy for fighting IPF: perspectives on a living drug.
    Wei Sun, Sirui Lu, Tao Chen, Yanrui He, Zuojun Xu, Zhigang Cai.
      Fibrotic interstitial lung disease (fILD), particularly idiopathic pulmonary fibrosis (IPF), represents an incurable progressive lung disorder characterized by a dismal prognosis. Fibroblasts constitute the principal cellular drivers of the fibrotic cascade. Although two pharmacological agents (pirfenidone and nintedanib) have secured regulatory approval for clinical application, they remain incapable of substantially attenuating disease progression. Persistent immune dysregulation driven alveolitis, occupies a critical upstream position in perpetuating fibroblast activation and extracellular matrix (ECM). Recent investigations have introduced an innovative strategy employing genetically engineered T cells to selectively target and eliminate activated fibroblasts. This approach involves generating chimeric antigen receptor (CAR) T cells in vivo by encapsulating mRNA encoding CARs within lipid nanoparticles (LNPs). These CAR T cells can specifically recognize and ablate fibroblasts expressing fibroblast activation protein (FAP). In this review, we summarize recently developed CAR T cell therapeutic strategies for IPF treatment with optimal targeting of FAP-fibroblasts, synthesize the existing preclinical studies and clinical trials evaluating anti-FAP CAR T cells to date, and critically discuss the adverse events associated with CAR T therapy alongside strategies to overcome current limitations of CAR T cell therapy in IPF management.
    Keywords:  CAR T cell; ILD; IPF; fILD; therapy
    DOI:  https://doi.org/10.3389/fimmu.2026.1770081
  5. Curr Opin Rheumatol. 2026 Mar 19.
    Cellular therapies for rheumatic disease.
    Fotios Koumpouras, Roberto Caricchio.
       PURPOSE OF REVIEW: Cellular therapies, particularly chimeric antigen receptor (CAR)-modified lymphocytes, have progressed from experimental oncology into serious consideration for selected autoimmune rheumatic diseases. Autologous and emerging allogeneic CAR-T platforms now offer the possibility of deep, drug-free remission in systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies (IIM), systemic sclerosis (SSc), and related conditions for which conventional therapies remain inadequate. This timely article reviews the rationale, current clinical experience, safety profile, and future directions of cell therapies in rheumatology with a focus on efficacy, safety, and "immune reset" in autoimmune rheumatic disease. The review is particularly pertinent as multiple parallel cell-based platforms (autologous and allogeneic CAR T cells, transient RNA CARs, CAR-NK, and T cell engagers) are entering the rheumatology space faster than practice guidelines or trial frameworks can fully adjust.
    RECENT FINDINGS: Recent studies show that CD19-directed CAR T cells can induce deep B-cell depletion with high rates of drug-free remission in refractory SLE and promising responses in SSc and IIM, accompanied by distinctive toxicity patterns such as mostly low-grade CRS, rare ICANS, and the newly described organ-specific LICATS. Parallel work demonstrates mechanistic "immune reset" (including type I IFN pathway suppression and naïve-skewed B-cell repopulation), expansion of indications to neurologic autoimmunity, emergence of off-the-shelf platforms (allogeneic CARs, γδ-CAR, CAR-NK, RNA CARs), and early human experience with CD19- and BCMA-directed T cell engagers in rheumatic disease.
    SUMMARY: Collectively, these findings position cellular therapies as powerful, potentially transformative options for highly selected patients with severe, refractory lupus and autoimmune rheumatic disease, but also underscore the need for disciplined trial design, long-term safety surveillance, and strategies to ensure equitable access.
    Keywords:  autoimmune rheumatic disease; bi-specific t-cell engagers; cellular therapies; chimeric antigen receptor T; systemic lupus erythematosus
    DOI:  https://doi.org/10.1097/BOR.0000000000001159
  6. Front Med (Lausanne). 2026 ;13 1787086
    Next-generation immune cell therapies for lung cancer: advances in CAR-T, NK, and TIL strategies.
    Anoud Khan, Amina Mujahid, Aryan Tareen, Ahrar Amin, Saqib Raza Khan, Danial Khan Hadi, Afsheen Raza.
      Lung cancer remains the leading cause of cancer-related mortality worldwide, and current therapies offer limited survival benefit for patients with advanced disease. While immune checkpoint inhibitors and targeted therapies have improved outcomes in some populations, most patients either fail to respond or develop acquired resistance, highlighting the need for more potent and durable immunotherapeutic strategies. Next-generation immune cell therapies, including chimeric antigen receptor T cells (CAR T), chimeric antigen receptor natural killer cells (CAR NK), and tumor-infiltrating lymphocytes (TIL), provide a promising approach for lung cancers that are refractory to conventional treatment. These therapies leverage the patient's own immune system or engineered immune cells to directly recognize and eliminate malignant cells, while potentially overcoming immunosuppressive tumor microenvironments. This review provides a comprehensive synthesis of recent advances in the design, engineering, and clinical development of CAR T, CAR NK, and TIL therapies in both non-small cell and small cell lung cancer. We discuss preclinical and early clinical studies demonstrating feasibility, safety, and mechanisms of action, including antigen targeting, immune cell persistence, trafficking, and intratumoral activity. Key challenges, such as tumor antigen heterogeneity, immune suppression, limited durability, and off-tumor toxicity, are critically evaluated. We also examine emerging strategies to enhance efficacy, including multi-antigen targeting, armored and logic-gated constructs, regional delivery, combination with checkpoint inhibition or other modulators, and scalable off-the-shelf manufacturing platforms. Collectively, these next-generation immune cell therapies represent a rapidly evolving and translationally relevant approach that may expand therapeutic options, improve survival, and provide durable antitumor responses in patients with lung cancer who have exhausted conventional therapies.
    Keywords:  chimeric antigen receptor T cells; chimeric antigen receptor natural killer cells; lung cancer; next generation immune cell therapies; tumor infiltrating lymphocytes
    DOI:  https://doi.org/10.3389/fmed.2026.1787086
  7. Crit Rev Oncol Hematol. 2026 Mar 15. pii: S1040-8428(26)00168-X. [Epub ahead of print]222 105281
    Rewiring immunity: CAR-T cells as a paradigm shift in hematologic oncology.
    Michael J Janes, Lei Zhao, Layne G Bruton, Aidan A Schmidt, Jacob M Parker, Mark R Wakefield, Yujiang Fang.
      Hematologic malignancies remain a significant public health concern in the United States, affecting over 1.5 million individuals. Although chemotherapy remains a foundational component of treatment, the emergence of novel therapeutic strategies has transformed the treatment landscape. This review examines the development, mechanism of action, expanding clinical applications, and barriers to care associated with chimeric antigen receptor T-cell (CAR T-cell) therapy. Relevant data was found via a literature search across major biomedical databases focusing on current clinical implementation of CAR T-cell therapies. To date, seven CAR T-cell therapies have received U.S. Food and Drug Administration approval, demonstrating robust response rates and effective clearance of malignant cells in hematologic malignancies, including B-cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia. Despite these promising outcomes, CAR T-cell therapy faces significant challenges, including manufacturing timelines, geographic access limitations, and substantial financial burden. As the field continues to evolve, this review aims to provide clinicians with an updated synthesis of clinical outcomes, treatment-related toxicities, and persistent barriers to equitable access.
    Keywords:  CAR-T cell; Cancer; Cancer therapies; Gene editing
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105281
  8. Transplant Cell Ther. 2026 Mar 17. pii: S2666-6367(26)00224-1. [Epub ahead of print]
    Statistical Methods for CAR-T cell Therapy Outcomes: A Review and Practical Considerations.
    Soyoung Kim, Kwang Woo Ahn, Brent Logan, Ruta Brazauskas, Min Chen, Marcelo C Pasquini, Amy Moskop.
      Chimeric antigen receptor T (CAR-T) cell therapy has been increasingly used as a cutting-edge treatment for blood cancers. The number of scientific articles focused on its outcomes is increasing. However, there is limited literature providing guidance on appropriate statistical analysis methods for CAR-T cell therapy studies. Statistical approaches applied to CAR-T cell therapy outcome analysis often use methods adopted from hematopoietic cell transplantation (HCT). There are important differences between these therapies which need to be accounted for in the outcomes analysis. Additionally, much of the literature on CAR-T cell therapy outcomes is focused on clinical trials which differ from real-world settings in long term follow up of these patients. There are some statistical challenges in analyzing CAR-T cell therapy data, such as defining patients' response to therapy and quantifying the duration of responses. While some outcomes such as overall survival and treatment-related mortality are seen in both HCT and CAR-T cell therapy studies, some post-therapy complications are unique to CAR-T cell therapies, and their statistical analysis should be given careful consideration. Other challenges include establishing appropriate time origin for each outcome, determining censoring time, and defining competing risks. Here, we propose to define common CAR-T cell therapy outcomes, appropriate statistical approaches for their analyses, and address these critical statistical challenges based on the observational data collected by the Center for International Blood and Marrow Transplant Research. We use observational data to illustrate these statistical methods for analyzing CAR-T cell therapy outcomes.
    Keywords:  Statistical methods; chimeric antigen receptor T-cell therapy
    DOI:  https://doi.org/10.1016/j.jtct.2026.03.016
  9. Cancer Gene Ther. 2026 Mar 15.
    Memory programming and new manufacturing paradigms in CAR-T cell therapy.
    Niloufar Mohammadkhani, Saber Ebrahimi, Marzieh Hesam Mohammadi, Tanja Nicole Hartmann, Mansour Poorebrahim.
      The therapeutic efficacy of chimeric antigen receptor (CAR) T cells is often constrained by their limited persistence in vivo. Accordingly, numerous strategies have been developed to prolong CAR-T cell survival, many of which leverage memory-like phenotypes to sustain anti-tumor activity. However, extended persistence can also exacerbate CAR-T cell-related toxicities in certain malignancies, underscoring the need for context-specific approaches. Moreover, the rapid advancement of "off-the-shelf" CAR-T platforms may diminish the necessity for engineering enhanced persistence, enabling timely and broadly accessible therapies. In this review, we discuss recent advances aimed at augmenting CAR-T cell persistence with an emphasis on memory-associated features, and highlight emerging technologies that promise to deliver ready-to-use CAR-T products while mitigating the need for further persistence-focused modifications.
    DOI:  https://doi.org/10.1038/s41417-026-01015-w
  10. Mol Ther Oncol. 2026 Jun 18. 34(2): 201171
    The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia.
    Alexandra Dreyzin, Flavia Gava, Chelsea Lamplugh, Julie Ma, Sara K Silbert.
      Chimeric antigen receptor (CAR) T cells have demonstrated remarkable ability to render multiple relapsed and refractory patients into a deep and often durable remission. Since initial FDA approval of tisagenlecleucel in 2017, real-world data have shown the benefit of this therapy, even among historically complex populations, such as infants, children with Down syndrome, and those with extramedullary leukemia. Despite the success of CAR T cell therapy, nearly half of patients tend to show relapsed disease, demanding ongoing advancements. Furthermore, the incorporation of the bispecific T cell engager, blinatumomab, into B cell acute lymphoblastic leukemia (B-ALL) therapy has fundamentally shifted the treatment paradigm, calling for a reevaluation of the optimal application of CAR T cells. In this review, we describe the current usage of CAR T cells in children, adolescents, and young adults (CAYAs) with B-ALL and discuss anticipated changes to CAR T cell therapy and post-infusion management. Upfront use of blinatumomab will require novel approaches to relapsed disease, including the use of CAR T cells earlier in therapy. Limited durability of the currently approved CAR T cells will require novel constructs along with improved toxicity mitigation and refinements in post-CAR disease surveillance and therapy. While CAR T cells have made an incredible impact on the field, there is much work due to improve outcomes for CAYAs with B-ALL.
    Keywords:  CAR T cells; MT: Special Issue - Advancements in pediatric cancer therapy; immunotherapy; pediatric B cell acute lymphoblastic leukemia; relapsed/refractory B cell acute lymphoblastic leukemia; targeted therapy
    DOI:  https://doi.org/10.1016/j.omton.2026.201171
  11. J Pharm Policy Pract. 2026 ;19(1): 2640252
    Regulatory and HTA framework for herbal medicines in Indonesia.
    Mohamad Kashuri, Taruna Ikrar, Rani Sauriasari, Vishnu Juwono, Arry Yanuar.
       Background: Herbal medicines are widely used in Indonesia and other LMICs, yet their integration into national health systems relies on coherent regulatory oversight, reliable evidence generation, functional pharmacovigilance (PV), and alignment with health technology assessment (HTA) and financing processes. Existing evidence varies in rigour and maturity, creating uncertainty for regulators and policymakers. A consolidated understanding of how available evidence informs regulatory, HTA, PV, and financing decisions is needed to guide a more predictable, evidence-informed governance framework for herbal medicines in Indonesia.
    Methods: An integrative review was conducted using Scopus, PubMed, Google Scholar, WHO IRIS, the ASEAN TMHS repository, and national regulatory portals for literature published between 2015 and 2025. Thirty-seven studies met eligibility and WHO-based methodological quality criteria. Data were extracted using a structured matrix, synthesised thematically, and deductively mapped to five analytic domains: evidence generation, regulatory pathways, HTA processes, pharmacovigilance systems, and financing-governance alignment.
    Results: Three system-level themes emerged. First, substantial misalignment exists between available evidence and regulatory requirements, driven by heterogeneous clinical methods, limited comparator data, and variable standardisation. Second, HTA remains weakly integrated into decision-making due to gaps in clinical effectiveness, limited economic evidence, and challenges in assessing multi-component interventions. Third, PV and governance systems show fragmentation, weak inter-agency coordination, and inadequate safety signal detection. These interdependent weaknesses reduce regulatory predictability, constrain HTA feasibility, and limit informed financing decisions.
    Conclusion: This review provides the first integrated synthesis of evidence generation, regulatory pathways, HTA processes, PV systems, and financing-governance alignment for herbal medicines in Indonesia. Findings highlight the need to strengthen evidence standards, adapt HTA methodologies, reinforce PV and laboratory capacity, and improve regulatory-financing linkages. Implementing the proposed framework can enhance policy coherence, regulatory transparency, and safety oversight, supporting more credible and evidence-informed integration of herbal medicines into Indonesia's health system.
    Keywords:  Evidence generation; health technology assessment; herbal medicines; pharmacovigilance; regulatory framework
    DOI:  https://doi.org/10.1080/20523211.2026.2640252
  12. Exp Hematol Oncol. 2026 Mar 19. pii: 34. [Epub ahead of print]15(1):
    Novel non-viral in vivo CAR-T therapies: latest updates from the 2025 ASH annual meeting.
    Bin Xue, Yifan Liu, Aibin Liang, Wenjun Zhang.
      The field of chimeric antigen receptor (CAR)-T cell therapy is undergoing a paradigm shift from complex ex vivo manufacturing to direct in vivo generation of CAR-T cells. This innovative approach leverages non-viral delivery platforms to reprogram a patient's own immune cells in situ, promising to overcome critical barriers of cost, scalability, and accessibility. The 2025 American Society of Hematology (ASH) Annual Meeting served as a showcase for groundbreaking preclinical data across a diverse array of non-viral technologies, including advanced lipid nanoparticles (LNPs), virus-like particles (VLPs), and polymeric nanoparticles. This correspondence summarizes the latest reports on these platforms, highlighting their potential to revolutionize the treatment of both autoimmune diseases and hematological malignancies.
    Keywords:  ASH 2025; CAR-T; In vivo; Lipid nanoparticles; Non-viral delivery
    DOI:  https://doi.org/10.1186/s40164-026-00765-5
  13. Crit Rev Oncol Hematol. 2026 Mar 14. pii: S1040-8428(26)00162-9. [Epub ahead of print]222 105275
    Progress and challenges in CAR-T cell therapy for bladder cancer.
    Kun Zhao, Zhongze Zhou, Xueming Ma, Xi Xiao, Long Cheng, Shuai Liu, Wenyun Wang, Zhilong Dong.
      Bladder cancer (BC) is a prevalent malignancy of the urinary system worldwide, with a rising global incidence, posing a significant threat to public health. The treatment of advanced and metastatic disease remains particularly challenging. Chimeric antigen receptor T-cell (CAR-T) immunotherapy has demonstrated remarkable efficacy in hematologic malignancies and is increasingly being explored in solid tumors. This review summarizes recent advances in CAR-T cell therapy for BC, focusing on major therapeutic targets, mechanisms of action, and potential combination strategies. Furthermore, we discuss findings from preclinical studies and early-phase clinical trials. Current evidence indicates that CAR-T therapy exhibits promising antitumor activity in BC. However, several critical challenges remain, including optimal target selection, the immunosuppressive tumor microenvironment (TME), and insufficient clinical validation. These findings may guide future translational and clinical investigations in this field.
    Keywords:  Bladder Cancer; CAR-T; Immunotherapy; Review; Therapeutic Targets
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105275
  14. bioRxiv. 2026 Mar 08. pii: 2026.03.05.709907. [Epub ahead of print]
    IL12-engineered human PSMA-CAR T cells for the treatment of advanced prostate cancer.
    Lupita S Lopez, Ziyou Cui, Yukiko Yamaguchi, John P Murad, Zhiyuan Yang, Ke Zou, Jason Yang, Wen-Chung Chang, Stephen J Forman, Vivien W Chan, Saul J Priceman.
      Adoptive cell therapies used to treat advanced prostate cancer are being developed to target several tumor-associated antigens, including prostate-specific membrane antigen (PSMA). Chimeric antigen receptor (CAR) T cell therapy using the single chain variable fragment (scFv) derived from the humanized murine mAb clone, J591, as the antigen-binding domain has shown promising anti-tumor activity. However, it has also been associated with macrophage activation syndrome and other unwanted toxicities, highlighting the need for more specific and human-derived antigen-binders with optimized construct designs for improved safety and efficacy. Here, we optimize a human scFv-based PSMA-targeted CAR (hPSMA-CAR) with highly selective PSMA targeting. We further introduce a membrane-bound IL-12 (mbIL12) molecule, which enhances potency with increased T cell expansion, IFNy production and anti-tumor cell activity in vitro . Using two clinically-relevant bone-metastatic prostate cancer models, we show that mbIL12-engineered hPSMA-CAR T cells drive potent in vivo anti-tumor responses. In summary, we have developed a promising therapeutic that has potential to promote safe and effective treatment of advanced PSMA+ prostate cancer.
    DOI:  https://doi.org/10.64898/2026.03.05.709907
  15. Rheumatology (Oxford). 2026 Mar 15. pii: keag126. [Epub ahead of print]
    Anti CD19 targeting CAR T cell therapy in ANCA-associated vasculitis.
    Luisa Schneider, Ann-Christin Pecher, Luca Hensen, Patrick Krumm, Rebekka Schairer, Kristina Reuß, Wolfgang Bethge, Claudia Lengerke, Joerg Henes.
       OBJECTIVES: To present a successful case study of anti-CD19 CAR T cell therapy in a patient with relapsing granulomatosis with polyangiitis (GPA).
    METHODS: A 69-year-old male patient suffering from relapsing GPA refractory to standardised immunosuppression underwent an experimental therapy involving CD19-targeting chimeric antigen receptor(CAR)T cells. The conditioning regimen consisted of fludarabine and cyclophosphamide. Follow-up intervals scheduled at one to three months' intervals, incorporated evaluations of the Birmingham Vasculitis Activity Score (BVAS), CT scans of the lungs, C-reactive protein (CRP), peripheral white blood cell count (WBC), lactate dehydrogenase, ANCA, immunoglobulin levels, post-CAR T cell treatment surveillance including (CAR)-lymphocyte counts.
    RESULTS: The patient was diagnosed with GPA involving the lungs in 2019. He showed a relapsed refractory disease course in spite treatment with rituximab, cyclophosphamide, avacopan, azathioprine, leflunomide and prednisolone. At presentation for CAR T cell treatment, the BVAS was 14, inflammation markers were elevated and pulmonary infiltrates were visible on the CT scan. CAR T cell therapy was well-tolerated with no cytokine release syndrome (CRS) or neurotoxicity, and led to rapid improvement of clinical condition, as well as radiological and laboratory test results. CAR T cells expanded with a transient peak but were not anymore detectable in the peripheral blood around day 90. In line, the significant B cell depletion and hypogammaglobulinemia observed post-treatment showed gradual recovery. At the latest follow-up 12-months post-treatment, the patient is in complete remission without further medication.
    CONCLUSION: CD19-targeted CAR T cell therapy was safe and efficacious in a patient with relapsed and refractory GPA. CAR T cell therapy has the potential to transform disease management and improve long-term outcomes for affected patients.
    Keywords:  CD19 CAR T cells; anca; autoimmune disorders; vasculitis
    DOI:  https://doi.org/10.1093/rheumatology/keag126
  16. Front Immunol. 2026 ;17 1761397
    Automated manufacturing of clinical-grade BDCA2 CAR NK cells in a closed system for the treatment of blastic plasmacytoid dendritic cell neoplasm.
    Rita Pfeifer, Sabine Müller, Marcus Nitsche, Melanie Sohmen, Julia Kostyra, Arthur Bister, Cathrin Bleilevens, Janina Brauner, Angela Mekes, Juliane Raasch, Dominika Lukas, Jens Kopatz, Wael Al Rawashdeh, Marsilius Mues, José Alberto Villacorta Hidalgo, Volker Huppert, Mario Assenmacher, Nina Möker, Rimas Orentas, Congcong Zhang.
      Recent progress in chimeric antigen receptor (CAR) natural killer (NK) cell therapy has demonstrated their promising potential in cancer immunotherapy. However, most current CAR NK cell manufacturing processes utilize open systems with multiple manual steps, making it challenging to maintain consistent therapeutic quality and regulatory compliance for clinical applications. We specifically developed blood dendritic cell antigen 2 (BDCA2)-targeting CAR NK cells for treating blastic plasmacytoid dendritic cell neoplasm (BPDCN). Here, we present an automated, current good manufacturing practice (cGMP)-compliant Natural Killer Cell Transduction (NKCT) process for producing clinical-grade CAR NK cells on the CliniMACS Prodigy® platform. This closed system integrates cell separation, activation, transduction, expansion, and harvest, thereby reducing contamination risks and ensuring cell product quality. The NKCT process achieved high transduction efficiency using baboon envelope pseudotyped lentiviral vectors (BaEV-LV) produced under cGMP conditions combined with Vectofusin®-1, yielding CAR NK cells with high viability and purity. Both in vitro and in vivo studies demonstrated the potent antitumor activity of CliniMACS Prodigy-manufactured BDCA2 CAR NK cells, highlighting a promising treatment strategy for BPDCN. In summary, this automated NKCT process enables both centralized and decentralized CAR NK manufacturing and facilitates the efficient clinical translation of CAR NK cell therapies.
    Keywords:  BDCA2 CAR; BPDCN; CAR NK cells; CliniMACS Prodigy NKCT; automated manufacturing; cancer immunotherapy
    DOI:  https://doi.org/10.3389/fimmu.2026.1761397
  17. Biomed Pharmacother. 2026 Mar 18. pii: S0753-3322(26)00253-2. [Epub ahead of print]198 119220
    Preclinical comparison of non-signaling domain in CD19 CAR T cell with interleukin-7 receptor alpha signaling domain.
    Pornlapat Keawvilai, Sirirut Jewmoung, Kristine Cate S Pe, Supannikar Tawinwung, Koramit Suppipat.
      Chimeric antigen receptor (CAR) T cells have emerged as an effective immunotherapy for hematologic malignancies. The non-signaling domain of CARs, comprising the spacer and transmembrane regions, is a key structural component that can be engineered to influence CAR expression and function. In this study, we evaluated three non-signaling domain configurations-IgG2.CH3/CD28, IgG2/CD28, and CD8/CD8-within a CD19 CAR construct incorporating 4-1BB and interleukin-7 receptor alpha (IL-7Rα) signaling domains. CARs incorporating the IgG2/CD28 domain exhibited reduced surface expression and diminished functional responses compared with IgG2.CH3/CD28 and CD8/CD8 constructs. The CD8/CD8 configuration supported the highest CAR expression and sustained surface density. In contrast, IgG2.CH3/CD28 CAR T cells displayed increased IL-2 and TNF-α secretion and enhanced CD107α upregulation following antigen stimulation. In a serial tumor cell rechallenge assay, IgG2.CH3/CD28 CAR T cells maintained cytotoxic activity and persistence compared with CD8/CD8 CAR T cells. In a NALM-6 xenograft model, IgG2.CH3/CD28 CAR T cells achieved durable tumor control and were associated with improved survival relative to CD8/CD8 CAR T cells. Collectively, these findings support the IgG2.CH3/CD28 non-signaling domain as a suitable structural component for CD19 CARs incorporating IL-7Rα signaling and provide insight into CAR design strategies aimed at improving T cell persistence and anti-leukemic activity.
    Keywords:  B-cell malignancies; CAR T cell; CD19; IL-7 receptor alpha (IL-7Rα); Non-signaling domain
    DOI:  https://doi.org/10.1016/j.biopha.2026.119220
  18. Med Sci (Paris). 2026 Mar;42(3): 311-314
    [In vivo CAR-Ts, a significant breakthrough].
    Bertrand Jordan.
      Since 2017, the CAR-T ex vivo approach has been very successful for the treatment of B cell malignancies in spite of its complexity and cost. A novel method involves transforming T lymphocytes into CAR-T cells in situ (therefore, in vivo) and promises simplicity, speed and affordability. It also seems applicable to several autoimmune diseases and is currently the object of much activity and interest in academic and corporate environments.
    DOI:  https://doi.org/10.1051/medsci/2026041
  19. Cancer Pathog Ther. 2026 Jul;4(4): 297-309
    Safety and efficacy of JWATM204, a novel Glypican-3 (GPC3)-targeted CAR T cell therapy for advanced hepatocellular carcinoma: A phase I dose-escalation study.
    Yongqiang Yang, Jing Tang, Zilong Wu, Jinfeng Zhang, Dongen Liu, Jun Fan, Gang Wu, Tao Zhang, Jun Xue.
       Background: Glypican-3 (GPC3) is an important therapeutic target for chimeric antigen receptor (CAR) T cell therapy in hepatocellular carcinoma (HCC). JWATM204 is a novel GPC3-targeted CAR T cell therapy developed on the Antibody Redirected T Cells with Endogenous Modular Immune Signaling (ARTEMIS) T-cell platform, combining the high affinity and specificity of an anti-GPC3 monoclonal antibody with enhanced safety profiles. This Phase I study aimed to evaluate the safety and tolerability of JWATM204 in patients with advanced HCC.
    Methods: This single-arm, single-center, open-label Phase I dose-escalation study enrolled patients with GPC3-positive advanced HCC refractory to prior anti-tumor therapy. Three doses of JWATM204 were used: 1 × 108, 3 × 108, and 10 × 108 cells. The endpoints included dose-limiting toxicities (DLTs), adverse events (AEs), pharmacokinetic parameters, and anti-tumor activity. Exploratory endpoints were predefined to evaluate potential biomarkers.
    Results: Six patients received an infusion of JWATM204, with two patients in each dose group. Only two instances of cytokine release syndrome (CRS) were observed, both were mild to moderate (Grade 2 and Grade 1, respectively), and resolved rapidly with standard management, demonstrating a favorable safety profile. No predefined DLTs were observed, and no cases of neurotoxicity or other serious treatment-related AEs occurred. Further dose escalation was not pursued due to strategic adjustments by collaborative partners and patient accrual challenges during the coronavirus disease 2019 (COVID-19) pandemic. Two patients achieved stable disease (SD; 33.3%; 95% confidence interval [CI], 5.9-70.0), while four experienced progressive disease (PD; 66.7%; 95% CI, 30.0%-94.1%), which yielded a disease control rate of 33.3% (95% CI, 5.9%-70.0%). As of the data cutoff date, one patient remained alive; three deaths were attributed to PD, one to COVID-19 co-infection, and one to intracranial hemorrhage. The median follow-up duration was 5.05 months (range, 3.00-25.90 months), with a median progression-free survival of 3.12 months (range, 2.07-5.77 months) and a median overall survival (OS) of 5.05 months (range, 3.00-25.90 months). The 6-month and 1-year OS rates were both 33.3% (95% CI, 5.9%-70.0%). Peripheral blood immune profiling suggested that patients with SD had higher proportions of natural killer (NK) cells both before and after treatment. RNA sequencing of pre-treatment tumor samples showed upregulated CRP and CYP2E1 expression in PD patients, which declined after therapy, suggesting potential links between inflammation and treatment response.
    Conclusions: JWATM204 demonstrated a favorable safety profile and showed preliminary anti-tumor activity in patients with advanced GPC3-positive HCC. Peripheral blood NK cell levels and tumor expression of CRP and CYP2E1 may serve as potential biomarkers for treatment response, providing a basis for further optimization of CAR T cell therapy in HCC.
    Trial registration: https://clinicaltrials.gov/; ID: NCT06144385.
    Keywords:  CAR T cell therapy; Glypican-3; Hepatocellular carcinoma; Immunotherapy; Safety
    DOI:  https://doi.org/10.1016/j.cpt.2025.12.002
  20. JCO Clin Cancer Inform. 2026 Mar;10 e2500308
    Cost-Effectiveness of Maintaining Higher Stem-Cell Collection Thresholds in the Chimeric Antigen Receptor T-Cell Era for Multiple Myeloma.
    Ehsan Malek, Brian Betts, Megan Herr, Marco Davila, Shernan Holtan, James J Driscoll, Han Yu.
       PURPOSE: Prolonged cytopenias are a common complication after chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma, increasing the risk of severe infection. Infusion of previously collected autologous stem cells may mitigate this risk, but the clinical and economic implications of proactive collection remain uncertain.
    METHODS: We developed an 8-year, monthly cycle Markov model simulating 10,000 patients undergoing CAR T therapy. Two strategies were compared: (1) no stem-cell boost and (2) availability of a boost for patients with prolonged cytopenias. Transition probabilities for neutropenia, infection, and infection-related mortality were derived from CARTITUDE-4 and published stem-cell boost reports. Costs included hospitalizations for severe infection and upfront stem-cell reserve collection. Deterministic and probabilistic sensitivity analyses were performed.
    RESULTS: In the base case, universal reserve collection reduced severe infections from approximately 650 to approximately 260 per 10,000 patients and averted approximately 50 infection-related deaths. However, average per-patient costs were higher in the boost arm (approximately $19,700 US dollars [USD] v $4,500 USD), reflecting a gross reserve collection cost of $17,918 USD per patient plus lower residual infection-related hospitalization costs. Survival outcomes were similar between arms, with relapse-related mortality dominating long-term outcomes. Sensitivity analyses confirmed robustness, with hospitalization cost and reserve collection cost identified as the most influential parameters.
    CONCLUSION: Proactive stem-cell collection for CAR T recipients reduces infectious complications and modestly improves infection-related survival but remains economically unfavorable when applied universally. A risk-adapted approach targeting patients at highest risk of prolonged cytopenias may better balance clinical benefit with cost-effectiveness.
    DOI:  https://doi.org/10.1200/CCI-25-00308
  21. Cureus. 2026 Mar;18(3): e105407
    China's Pharmaceutical Ascent: Opportunity for Global Health, Test for US Leadership.
    Arya Babul, Parisa Mahdavi, Momina Hussain, Najib Babul.
      Diseases know no borders; neither should the solutions.  - Sir George Alleyne, Address to the Pan American Health Organization, 1998 China's rapid expansion in pharmaceutical innovation has prompted analyses that variously portray this rise as a geographic shift, a regulatory challenge, or a geopolitical threat. Drawing on recent contributions from Kinch et al., Vokinger et al., Gautam, and Gottlieb, this commentary examines how broader discussions of China's rise often conflate geography with geopolitics, obscuring the more consequential structural transformation underway in global drug discovery, development, and regulation. China's ascent reflects regulatory reform, AI‑enabled discovery, and the out‑licensing of high‑value clinical assets that increasingly shape multinational R&D pipelines. Although geopolitical tensions around data integrity and market access are real, they should not eclipse opportunities for regulatory cooperation, shared standards, and improved patient access. Meanwhile, US vulnerabilities arise less from China's progress than from domestic policy decisions that weaken scientific capacity and global health partnerships. A structural, evidence‑based framing, rather than one rooted in rivalry, offers a more constructive foundation for policy, emphasizing regulatory quality and sustained investment in US biomedical infrastructure. The organizing principle for global drug innovation should be health, not geopolitical competition.
    Keywords:  ai‑enabled drug discovery; china pharmaceutical innovation; fda regulatory policy; global drug development; nmpa; out‑licensing; pharmaceutical regulation; public health policy; regulatory harmonization; us-china relationship
    DOI:  https://doi.org/10.7759/cureus.105407
  22. Cardiol Rev. 2026 Mar 16.
    Second-Generation and Off-the-Shelf CAR Platforms: Emerging Cardiovascular Implications of Next-Generation Cellular Immunotherapies.
    Jatin Thukral, Pyush Moudgil, Abhay Mann, Tanish Goyal, Ninaad Sindhwani, Riya Kaushal Shah, Kanishka Uttam Chandani, Harbir Kaur, Nikhil Thukral, Maharshi Raval, Siddharth Pravin Agrawal, William H Frishman, Wilbert S Aronow.
      Chimeric antigen receptor (CAR)-based therapies have become an integral part of modern cancer care, delivering durable responses in patients with otherwise refractory hematologic malignancies. As their use has expanded, it has become increasingly clear that these immune-based treatments exert important effects on the cardiovascular system. Rather than reflecting isolated cardiac injury, CAR-associated cardiovascular complications arise from a broader inflammatory process in which immune activation, cytokine release, endothelial dysfunction, and myocardial stress are closely interconnected. Pro-inflammatory mediators such as interleukin-6, interleukin-1β, tumor necrosis factor-α, and interferon-γ play central roles in shaping these responses, particularly during cytokine release syndrome. From a clinical perspective, cardiovascular manifestations often include hypotension, arrhythmias, and transient reductions in left ventricular function, with more severe presentations occurring in patients who develop high-grade inflammatory toxicity. At the same time, advances in immune engineering are reshaping how these platforms are viewed, extending their relevance beyond toxicity alone. Preclinical studies now suggest that CAR-based approaches may be adapted to modulate cardiac fibrosis and promote myocardial repair, highlighting a potential shift from purely oncologic applications toward broader cardiovascular benefit. Placing these developments within a cardio-oncology framework emphasizes the need for careful cardiovascular assessment, longitudinal monitoring, and close collaboration between specialties.
    Keywords:  CAR T-cell therapy; cardio-oncology; cardiovascular risk stratification; chimeric antigen receptor therapy; cytokine release syndrome; endothelial dysfunction; immune effector cell therapies; immune-mediated cardiotoxicity; myocardial injury; translational cardio-immunology
    DOI:  https://doi.org/10.1097/CRD.0000000000001237
  23. Curr Rev Clin Exp Pharmacol. 2026 Mar 10.
    The Significance of Model-Based Strategies in Drug Development throughout the Lifecycle and Regulatory Decision-Making.
    Maitry Suthar, Neha Dandekar, Dipti Patel, Drashti Shah.
       INTRODUCTION: Model-informed drug development (MIDD) is a regulatory-endorsed approach that streamlines drug discovery, development, and approval. Actively promoted by the U.S. Food and Drug Administration (FDA), it integrates quantitative modelling to support decision-making across drugs, generics, and biologics.
    OBJECTIVES: This study aims to highlight the applications, benefits, and future perspectives of MIDD in optimizing clinical trial design, supporting regulatory review, advancing biopharmaceutics, and enabling innovation in emerging therapeutic areas.
    METHODS: Current applications of MIDD were evaluated, focusing on its role in new drug development, generic drug approval, biopharmaceutics, and early exploration in cell and gene therapy. The study emphasizes computational modelling, dose optimization, clinical trial refinement, and postapproval lifecycle management strategies.
    RESULTS: MIDD has demonstrated considerable impact in optimizing dose selection, refining trial design, and addressing regulatory concerns regarding efficacy and safety. In the field of biopharmaceutics, computational modelling has guided formulation development and facilitated subsequent in vivo studies. In genetics, mathematical modelling has enabled efficient development and approval of complex formulations, reducing both time and cost. MIDD shows strong potential for quantitatively analysing biological activity, pharmacodynamics, transgene expression, immune responses, safety, and therapeutic effectiveness.
    CONCLUSION: MIDD is a transformative approach in drug development, offering robust tools for decision- making and regulatory assessment. Its broader implications across therapeutic domains are expected to enhance innovation, improve patient outcomes, and reduce development costs. Future advancements, particularly in cell and gene therapy, will further expand its role as a cornerstone of drug development.
    Keywords:  Biopharmaceutics; computational modeling.; gene therapy; generic drugs; model-informed drug development
    DOI:  https://doi.org/10.2174/0127724328406757251204044645
  24. Sci Rep. 2026 Mar 17.
    A targeting lentiviral vector for generation of CAR-T cells in vivo.
    Muhadasi Tuerxunyiming, Jianguo Michael Yin, Ping Zhu, Maoxuan Liu, Zheng Fu, Qing Zhao.
      Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable therapeutic efficacy in treating cancer and autoimmune diseases. However, current CAR-T cell therapy requires ex vivo T cell engineering, which is both time-consuming and cost-prohibitive, adding complexity to the overall treatment. In this study, using an engineered Sindbis virus envelope, we developed a lentiviral vector system with high specificity for targeting human T cell line and primary T cells, but not targeting other immune cell subsets. Notably, this T cell-specific lentiviral vector does not require additional anti-CD3/CD28 stimulation for primary T cell activation during infection in vitro. Furthermore, the lentiviral vector successfully delivered a CD19-targeting CAR molecule to human primary T cells in vivo. The in vivo generated CD19-CAR-T cells efficiently mediated B cell lymphoma clearance. Overall, our study provides a promising tool for the development of in vivo T cell engineering approaches.
    Keywords:  CAR-T; Chimeric antigen receptor; In vivo; Lentiviral vector
    DOI:  https://doi.org/10.1038/s41598-025-17342-1
  25. Immunol Cell Biol. 2026 Mar 15.
    One lineage, many diseases: γδ T cells as context-dependent immune surveyors.
    Lauren J Howson.
      Key highights from studies of γδ T cells in 2025 reveal new insights into their role in infection, inflammation and allergy and the impact of cellular and metabolic stress on γδ T cells. Created in BioRender. Howson, L. (2026) https://BioRender.com/mhdcqha.
    DOI:  https://doi.org/10.1111/imcb.70103
  26. Front Pediatr. 2026 ;14 1742663
    Progress of biological agents and CAR cell therapy in the treatment of common autoimmune diseases in children.
    Qi-Ling Yin, You-Qiong Liu, Hui-Min Zhang, Yu-Dong Gao, Ying Wang, Wei-Hua Zhang.
      Autoimmune diseases are characterized by immune disorders that lead to abnormal activation of autoreactive immune cells, which in turn lead to tissue destruction and organ dysfunction. Compared with adults, autoimmune diseases in children are more severe, with increased disease activity and organ damage occurring earlier, and with higher mortality. In addition to the poor effect of traditional therapy in some children, children also have the needs for growth and development, and the use of traditional therapy will lead to severe immunosuppression and sequelae, affecting the quality of life of children. The emergence of Chimeric antigen receptors (CAR) cell therapy and biological agents has provided new treatment options for children with autoimmune diseases.
    Keywords:  CAR cell therapy; autoimmune diseases; biological agents; children; immunomodulatory agents
    DOI:  https://doi.org/10.3389/fped.2026.1742663
  27. Front Immunol. 2026 ;17 1679175
    Emapalumab in pediatric patients with high-grade cytokine release syndrome associated with CAR T-cell therapy.
    Jing Zhang, Wenhua Shi, Jing Yang, Juan Qian, Meng Su, Kang An, Tianyi Wang, Rujun Jia, Chengming Fei, Yanjing Tang, Benshang Li.
       Background: Chimeric antigen receptor T (CAR-T) cell therapy significantly improves the prognosis of a variety of hematological malignancies; however, its broader application in clinical practice is hindered by adverse events, particularly cytokine release syndrome (CRS). Moreover, the selection of treatment strategies for patients with high-grade CRS must be meticulously tailored. Emapalumab, a fully human IgG1 monoclonal antibody targeting IFN-γ, has been proposed to have clinical benefit in CRS.
    Methods: In this retrospective study, we conducted a comprehensive analysis of clinical and laboratory parameters in 38 pediatric patients who failed low-dose glucocorticoids monotherapy, tocilizumab monotherapy or glucocorticoid-tocilizumab combination therapy, following treatment with investigational CAR-T products.
    Results: Emapalumab significantly improved both clinical symptoms and laboratory parameters. The rapid decrease in mean temperature (39.61 vs. 38.38°C, P < 0.001) and levels of inflammatory markers including IL-2 (32.35 vs. 11.94 pg/ml, P < 0.001), IL-10 (222.29 vs. 86.09 pg/ml, P = 0.018), TNF-α (4.17 vs. 2.94 pg/ml, P = 0.032), and IFN-γ (21984.11 vs. 674.87 pg/ml, P < 0.001) indicated the remarkable scavenging efficacy of emapalumab against cytokine storm following CAR-T therapy. Additionally, both mean CAR-T cell counts (549.95 vs. 8.16 cell/μl, P < 0.001) and the ratio of CAR-T to CD3+ (11.3% vs. 36.54%, P < 0.001) in peripheral blood increased significantly, demonstrating that the administration of emapalumab didn't seem to have a significant negative impact on the proliferation of CAR-T cells. The median EFS and OS were both not reached, with an EFS rate of 76.9% (95%CI, 63.8-92.6) and with an OS rate of 80.1% (95% CI, 67.7-94.6) at 6 months. Throughout the treatment course, no direct evidence of emapalumab-related safety risks was observed.
    Conclusion: Emapalumab seems to serve as an effective salvage therapy for patients experiencing high-grade CRS with inadequate response to low-dose glucocorticoids and/or tocilizumab following CAR-T therapy. These data supported the use of emapalumab in high-grade CRS as well as provide rationale for future prospective studies.
    Keywords:  IFN-γ; chimeric antigen receptor T-cell; cytokine release syndrome; efficacy; emapalumab; safety
    DOI:  https://doi.org/10.3389/fimmu.2026.1679175
  28. Biomed Pharmacother. 2026 Mar 18. pii: S0753-3322(26)00292-1. [Epub ahead of print]198 119259
    Immune checkpoint targeted drug conjugate therapies: Bridging preclinical and clinical innovation for solid tumor therapy.
    Waleed H Almalki.
      Solid tumors remain a significant therapeutic challenge due to their complex biology, heterogeneous tumor microenvironment (TME), and frequent development of resistance to standard treatments. Although immune checkpoint inhibitors (ICIs) have redefined tumor therapy by restoring antitumor immunity, their clinical benefit in Solid tumors is often constrained by low response rates (LRR), immune-related toxicities, and adaptive resistance. Immune checkpoint targeting drug conjugates (IDCs) have recently emerged as an innovative approach that combines checkpoint blockade with the targeted delivery of cytotoxic or immunomodulatory payloads. By employing monoclonal antibodies (MABs) or engineered scaffolds conjugated to potent effector molecules through optimized linker chemistries, IDCs are designed to improve tumor selectivity, reinvigorate T-cell activity, and induce direct tumor cell death. This review outlines the design principles, operational mechanism, and current clinical and preclinical (PC) progress of IDCs in Solid tumors, with emphasis on key targets including PD-L1/PD-1, TIGIT, CTLA-4, and LAG-3. Translational challenges, including safety concerns, resistance pathways, and manufacturing complexities, are also examined, alongside emerging innovations such as bispecific formats and rational combination strategies. Collectively, IDCs represent a promising next-generation modality with the potential to expand durable therapeutic outcomes in solid tumor management.
    Keywords:  Drug conjugates; Immune check point inhibitors; Immunotherapy; Monoclonal antibodies; Solid tumors
    DOI:  https://doi.org/10.1016/j.biopha.2026.119259
  29. Drug Des Devel Ther. 2026 ;20 588295
    Artificial Intelligence as a Disruptive Force in Pharmaceutical Innovation: Transforming Discovery, Development, and Manufacturing.
    Yedi Herdiana, Ahmed Fouad Abdelwahab Mohammed, Angga Prawira Kautsar, Iyan Sopyan, Nasrul Wathoni.
      Artificial Intelligence (AI) is increasingly being implemented in pharmaceutical sciences and has the potential to improve efficiency across the value chain, from drug candidate discovery to manufacturing, quality monitoring, and regulatory process support. Nonetheless, the integration of AI within the pharmaceutical sector encounters persistent obstacles, such as data interoperability and fragmentation, the necessity for model validation and governance to satisfy compliance standards, the potential for bias and accountability concerns, and deficiencies in workforce skills. This review consolidates significant advancements in AI applications, such as generative AI, laboratory automation, and the digital twin concept, highlighting that effective implementation relies on workflow integration, data quality and integrity, and sufficient human-in-the-loop mechanisms. We propose strategic recommendations centred on human resource readiness, governance structures, and technology maturity assessment to assist readers in differentiating feasible solutions from aspirational frameworks. Moving forward, research and adoption will likely highlight precision medicine and regulatory-industry collaboration mechanisms for AI evaluation. The integration of AI with supporting technologies such as tamper-evident provenance/audit layers (such as blockchain) remains exploratory and generally limited to pilots.
    Keywords:  closed-loop discovery; digital twins in healthcare; generative ai in drug discovery; pharma 4.0; self-driving laboratories
    DOI:  https://doi.org/10.2147/DDDT.S588295
  30. J Nanobiotechnology. 2026 Mar 17.
    Engineering BiTE-inspired IPSC-exosomes to potentiate CAR-T cell therapy against lung cancer.
    Ronghao Wang, Guining Fu, Haozhao Dou, Mingyuan Hu, Zhanglin Li, Junwen Gan, Jiasheng He, Xiaojian Li, Guihong Zhang, Xianjun Li, Tianchuan Zhu, Qingdong Cao.
      Chimeric antigen receptor T (CAR-T) cell therapy faces critical barriers in solid tumors, including poor infiltration, T cell exhaustion, and immunosuppressive microenvironments, resulting in response rates below 10%. Herein, we engineered an inhalable nanoplatform using induced pluripotent stem cell-derived exosomes (IEXOs) displaying bispecific PD-1/mesothelin (MSLN) single-chain variable fragments (scFv) and loaded with indole-3-propionic acid (IPA) for metabolic reprogramming. IEXOs demonstrated high yield and intrinsic antitumor properties, inhibiting Lewis lung carcinoma (LLC) cell proliferation and migration. The bispecific exosomes loaded with IPA (BIEXO@IPA) achieved efficient pulmonary delivery via nebulization with 79.3% tumor cell-specific uptake versus 47.9% for liposomes in orthotopic lung cancer models. BIEXO@IPA treatment reduced tumor burden by 87.9% and achieved 80% survival at 80 days. Mechanistically, BIEXO@IPA bridged PD-1+ T cells to MSLN+ tumor cells through bispecific engagement while expanding progenitor exhausted T (Tpex) cells and reducing regulatory T cells. When combined with CAR-T cells, BIEXO@IPA achieved 66.7% complete remission with 100% survival at 80 days and 83.3% resistance to tumor rechallenge. Safety assessments revealed minimal toxicity. This BIEXO@IPA platform represents a scalable, clinically translatable strategy that addresses fundamental CAR-T limitations in solid tumors through synergistic multimodal immunomodulation.
    Keywords:  Bispecific T cell engagers; Chimeric antigen receptor T cells; Exosomes; Immunotherapy; Indole-3-propionic acid; Induced pluripotent stem cells; Lung cancer
    DOI:  https://doi.org/10.1186/s12951-026-04242-3
  31. Mol Ther Nucleic Acids. 2026 Mar 12. 37(1): 102805
    mRNA-based CAR T cell engineering: Unmodified mRNA enables high CAR expression without innate immune activation in T cells.
    Nourhan Kahwaji, Niklas Kotzian, Jasmin Melissa Prinz, Yaolin Pu, Jonas Kath, Samira Picht, Anna Luisa Hiller, Antonia Klaas, Charlotte Maeve Dunne, Michael Launspach, Andriko Palmowski, Arnd Kleyer, David Nils Simon, Dimitrios Laurin Wagner, Chantal Pichon, Gerhard Krönke, Michael Schmueck-Henneresse, Hans-Dieter Volk, Manfred Gossen, Norman Michael Drzeniek.
      Unmodified, uridine-containing mRNA is known to trigger antiviral immune responses, inflammatory signaling, and apoptosis in transfected cells. To avoid this and enable high expression, modified nucleosides such as N1-methylpseudouridine have become the gold standard for mRNA applications including T cell engineering, albeit at increased cost. Here, immune responses toward mRNA were evaluated across five primary human cell types. Remarkably, T cells, unlike other immune and non-immune cell types tested, exhibited no immune activation by unmodified mRNA. T cell viability and cytokine secretion remained unaffected, regardless of mRNA delivery method via lipid nanoparticles or electroporation. The absence of nucleotide modifications improved expression of chimeric antigen receptor (CAR) in activated T cells and CAR-T cell cytotoxic potency. By eliminating the need for mRNA-nucleoside modification in CAR-T cell engineering, our findings challenge existing paradigms and position mRNA as a non-inflammatory, minimally invasive and highly efficient tool for T cell engineering, while simplifying and reducing manufacturing cost.
    Keywords:  CAR t cells; DNA-free CAR T manufacturing; MT: Oligonucleotides: Therapies and Applications; N1-methylpseudouridine; T cell engineering; chimeric antigen receptor; immunogenicity; innate immune activation; lipid nanoparticles; messenger RNA; nonviral gene transfer; nucleoside modifications; toll-like receptor; unmodified mRNA; uridine
    DOI:  https://doi.org/10.1016/j.omtn.2025.102805
  32. Front Microbiomes. 2025 ;4 1553243
    The role of gut microbiota in autoimmune disease progression and therapy: a comprehensive synthesis.
    Mohammad Adawi.
      Autoimmune diseases arise from the immune system's dysregulated attack on the body's own tissues, influenced by a complex interplay of genetics, environment, and the microbiome. This comprehensive review and meta-analysis examines the dynamic relationship between gut microbiota and autoimmune diseases, highlighting their role in disease onset, progression, and potential therapeutic interventions. Emerging evidence underscores the bidirectional interactions between microbiota and immune pathways, particularly through mechanisms like mucosal immune modulation and regulatory T-cell activity. Microbiota dysbiosis, characterized by altered diversity and function, is consistently associated with autoimmune conditions such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. The review identifies critical microbiota-driven factors, including antigenic mimicry and inflammatory signaling pathways that disrupt immune tolerance and exacerbate autoimmunity. Meta-analysis findings reveal a consistent reduction in microbial diversity across autoimmune diseases, emphasizing the role of specific taxa and their metabolites in influencing disease severity and immune responses. Therapeutic strategies, such as probiotics, prebiotics, and microbiome-targeted interventions, offer promising avenues to restore microbiome balance and mitigate autoimmune inflammation. Despite significant advances, challenges in methodology, limited longitudinal studies, and heterogeneity in results highlight the need for standardized research protocols and larger, well-controlled clinical trials. Future studies should prioritize personalized approaches to microbiome modulation, integrating dietary, genetic, and environmental factors to improve disease management and prevention. This work consolidates current knowledge, providing a framework for future research and clinical applications in the field of microbiome-autoimmune interactions.
    Keywords:  autoimmune diseases; dysbiosis; gut microbiome; immune regulation; microbiome-targeted therapy
    DOI:  https://doi.org/10.3389/frmbi.2025.1553243
  33. Crit Rev Oncol Hematol. 2026 Mar 14. pii: S1040-8428(26)00167-8. [Epub ahead of print]222 105280
    The gut-tumor metabolic axis: A comprehensive exploration of bidirectional crosstalk in cancer immunotherapy.
    Vincent Kawuribi, Aaron Awere-Duodu, Franklin A Adjei, Abdul-Halim Osman, Herman Bomansaan, Martin Mussa Madadi, Joseph Umar Tampuri, Joseph Adu-Amankwaah.
      The gut-tumor metabolic axis represents a bidirectional immunometabolic network in which tumor-derived metabolites reshape microbial ecology, while gut microbiome-derived metabolites recalibrate systemic and intratumoral immunity, ultimately influencing cancer progression and immunotherapy outcomes. Tumor aerobic glycolysis generates excess lactate and acidity that suppress cytotoxic immune function, remodel the tumor immune microenvironment, and indirectly perturb intestinal microbial composition. In turn, microbial metabolites including short-chain fatty acids, bile acid derivatives, tryptophan catabolites, inosine, and trimethylamine N-oxide signal through defined host pathways such as GPR109A, AHR, and adenosine A2A receptors to regulate antigen presentation, T-cell differentiation, macrophage polarization, and immune checkpoint sensitivity. Preclinical and emerging clinical evidence demonstrates that dietary modulation, rational probiotics, and fecal microbiota transplantation can enhance immune checkpoint inhibitor efficacy in selected contexts. However, metabolite effects are highly context dependent, with dose, timing, tumor type, and immune state critically shaping therapeutic benefit or resistance. This review integrates mechanistic insights and clinical evidence, highlights translational challenges including safety, donor heterogeneity, and biomarker validation, and proposes a framework for biomarker-guided microbiome-based strategies to advance precision cancer immunotherapy.
    Keywords:  Gut microbiome; Immunotherapy; Metabolites; Precision medicine; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105280
  34. Nat Biotechnol. 2026 Mar;44(3): 335
    New rules spur cell and gene therapy trials in China.
      
    DOI:  https://doi.org/10.1038/s41587-026-03065-9
  35. Rev Bras Enferm. 2026 ;pii: S0034-71672026000101005. [Epub ahead of print]79 e20250157
    Expert participation in the health technology assessment process: a scoping review.
    Sandra Maria Dos Santos Figueiredo, Fernanda de Nazaré Almeida Costa, Marcia Helena Machado Nascimento, Cristiane Cardoso de Paula, Liane Bahú Machado, Eliana Rosa da Fonseca, Elizabeth Teixeira.
       OBJECTIVES: to map evidence on specialist participation in the health technology assessment process.
    METHODS: a scoping review was conducted using the JBI method, searching the MEDLINE/PubMed, Scopus, EMBASE/Elsevier, WoS/Clarivate, CINAHL, ASP/EBSCO, APA PsycINFO, ERIC, LILACS/BVS, SciELO, and INAHTA databases. Original articles published between 2013 and 2023 were considered. Data were extracted from 89 studies and analyzed using descriptive statistics.
    RESULTS: between three and 15 specialists (64% of studies) participated. The property attribute was assessed for digital and non-digital devices, management systems, and equipment (93.1%, 94.2%, 60%, 33.3%, respectively), the cost-effectiveness attribute, for medications (60%), and the utility attribute, for medical-surgical procedures (31.6%). Participation was online, using digital and non-digital devices (53% and 52%, respectively), in-person, using devices (77.7%), and mixed, for the other types.
    CONCLUSIONS: it is necessary to structure the assessment according to the specific characteristics of the technology type, providing insights for implementing innovations in this sector.
    DOI:  https://doi.org/10.1590/0034-7167-2025-0157
  36. Arch Public Health. 2026 Mar 20.
    What patients value in data reuse for oncology research: a multi-stakeholder qualitative study to inform the European Health Data Space implementation in Belgium and beyond.
    Teodora Lalova-Spinks, Ine van Zeeland, Silke Léonard, Florence Horicks, Brent Taels, Patricia Cervera de la Cruz, Lyzette Bax, Bernard Carton, Willy Dirkx, Mahsa Shabani.
      
    Keywords:  Data protection; EU health policy; European Health Data Space; Health research; Oncology research; Patient involvement; Patient value; Secondary use of data
    DOI:  https://doi.org/10.1186/s13690-026-01884-5
  37. J Biol Eng. 2026 Mar 20.
    Are we there yet? The road to faster and more efficient CAR T cell manufacturing.
    Leonor N Matos, Margarida S Costa, Margarida Serra, Marta H G Costa.
      
    Keywords:  Bioprocess control; Bioprocess parameters; CAR T cell; Point‑of‑care manufacturing; Rapid manufacturing; Stem-like CAR T cells
    DOI:  https://doi.org/10.1186/s13036-026-00666-5
  38. Transpl Immunol. 2026 Mar 18. pii: S0966-3274(26)00040-7. [Epub ahead of print] 102382
    T-cell receptor-engineered T cells (TCR-e T cells): A novel cellular therapy for hematopoietic malignancies?
    Kajetan Karaszewski, Wiesław Wiktor Jędrzejczak.
      Despite the undeniable successes of chimeric antigen receptor T cells in the treatment of numerous hematopoietic malignancies, instances in which this therapy shows limited effectiveness, such as in acute myeloid leukemia (AML), still exists. This situation has prompted a search for alternative cellular therapies for neoplastic diseases. T-cell receptor-engineered T cells (TCR-e T cells) represent another approach to cellular cancer therapy that relies on the genetic modifications of lymphocytes. They are designed to interact with endoplasmic tumor-associated antigens (TAAs) presented on the cell surface via the major histocompatibility complex. Hence, the therapeutic effect is restricted to individuals with a specific TAA overexpression in the context of particular human leukocyte antigen types. Although promising results and the first approvals of TCR-e T cells for the treatment of solid tumors have been reported, only a few phase I/II clinical trials have been registered in hematopoietic malignancies, and some were terminated before yielding conclusive results. The most investigated TAAs as targets for TCR-e T cells in hematopoietic malignancies include Wilms tumor 1 (WT1), preferentially expressed antigen in melanoma (PRAME), and minor histocompatibility antigen (MiHA) in patients with AML. Similarly, New York esophageal squamous carcinoma 1 (NY-ESO-1) and B-cell-specific coactivator OBF-1 (BOB1) markers have been targeted in patients with multiple myeloma. With promising preliminary results, TCR-e T cell therapies targeting WT1, PRAME, MiHA, NY-ESO-1, and BOB1 remain under development as therapeutic options for hematologic malignancies.
    Keywords:  Acute myeloid leukemia; Cellular therapy; Hematology; Multiple myeloma; TCR engineered T cells
    DOI:  https://doi.org/10.1016/j.trim.2026.102382
  39. JMIR Med Inform. 2026 Mar 18. 14 e80435
    Digital Public Reporting Systems for Evaluating Health Care Quality: Systematic Review.
    Lanmei Du, Reima Suomi, Elorm Damalie.
       Background: Health care public reporting (PR) refers to making information about the quality and performance of health care providers available to the public. The primary targeted use of PR is the selection of a health care provider. Previous studies suggest that PR has improved health care quality; however, the overall adoption rate of PR systems remains low. Misalignment between PR information and users' actual needs can explain this gap.
    Objective: This study conducts a systematic literature review of PR systems in health care, aiming to explore how data encoding and presentation influence user utilization, with particular attention to the impact of data inconsistencies and inaccuracies on actual use.
    Methods: A literature search was conducted on 5 electronic databases (Web of Science, CINAHL, Embase, PsycINFO, and PubMed), focusing on studies providing information in health care from an individual perspective. Subsequently, the quality of the included studies was assessed using the Mixed Methods Appraisal Tool (McGill University). Finally, a total of 25 empirical studies were included in this study.
    Results: Among the 25 studies, 40% (10/25) investigated website presentation formats, 20% (5/25) explored dashboard-based data presentation formats in PR systems, 48% (12/25) examined data quality, and 20% (5/25) addressed user heterogeneity. Quantitative methods were used in 80% (20/25) of studies, while qualitative and mixed method designs accounted for 16% (4/25) and 4% (1/25), respectively. Findings suggest that standardized website and dashboard guidelines improve data reliability and user comprehension and that user heterogeneity mediates the effects of structural and process indicators on outcomes. Data collection was completed in February 2025, and the study was projected to be fully completed by September 2025.
    Conclusions: This study provides an integrated structure-process-outcome-based framework for PR in health care. By presenting data through dashboards, inconsistencies and inaccuracies in data across different web pages can be mitigated, thereby decreasing conflicting information and improving comprehension in PR systems. Based on the literature findings and identified knowledge gaps, this study also proposes future research directions for online PR.
    Keywords:  data and information process; digital health; health literacy; public reporting systems; quality indicators
    DOI:  https://doi.org/10.2196/80435
  40. Mol Biotechnol. 2026 Mar 16.
    CRISPR-Cas9: Genome Engineering and Future Vaccine Applications.
    Masoumeh Madhi, Pourya Gholizadeh.
      The CRISPR-Cas9 system, a transformative genome engineering tool derived from prokaryotic adaptive immunity, is reshaping the landscape of biological research and therapeutic development. This review provides a critical synthesis of its rapidly evolving, yet underexplored, application in rational vaccine design. We analyze how CRISPR-Cas9 and its derivative platforms (including base editing, prime editing, and CRISPRi/a) are being repurposed from therapeutic gene editing to become indispensable assets in vaccinology. This transition is powered by the convergence of CRISPR-mediated precision with synthetic biology, enabling the rapid engineering of novel vaccine vectors and attenuated strains, the precise optimization of antigen sequences for enhanced breadth and potency, and the direct modulation of host immune responses. Notwithstanding this potential, significant technical and translational hurdles persist, including off-target editing risks, delivery inefficiencies in vivo, and unresolved regulatory pathways for genetically modified vaccines. We detail these mechanisms and evaluate the current preclinical and clinical landscape, while addressing persistent challenges in safety, delivery, and scalability. By delineating these advances and obstacles, this review outlines a forward-looking framework for leveraging CRISPR technology to create programmable, precision vaccines against emerging and re-emerging pathogens, moving the field beyond empirical methods toward a new paradigm of rational immunization.
    Keywords:  CRISPR-Cas9; Gene therapy; Genome editing; Precision medicine; Vaccine development
    DOI:  https://doi.org/10.1007/s12033-026-01563-4
  41. Ther Innov Regul Sci. 2026 Mar 15.
    Regulatory Approaches to Electronic Labelling in the USA, EU, and India: A Comparative Overview.
    Komal Saini, Ramandeep Singh.
       OBJECTIVE: In this era of growth, e-labelling is becoming increasingly important as the labels are important sources of information for patients. However, regulations governing e-labeling for pharmaceuticals and medical equipment varies throughout the countries. This review compares the e-labelling regulation approaches in EU, USA, and India.
    SCOPE: The regulations have been initiated by appropriate governments and/or health authorities of EU, USA, and India in collaboration with key stakeholders, including patients, healthcare providers, pharmaceutical companies, environmental and regulatory agencies. EU and USA have established the digital labelling but India still relies on paper instruction manuals with limited digital systems.
    METHODOLOGY: The regulatory information and current trends of e-labelling in EU, US, and India were studied and compared for electronic prescribing and electronic decision support systems with health record. Regulatory information was recognized through a structured review of official regulatory agency websites (FDA, EMA, CDSCO), international organizations (WHO, ICH), and peer-reviewed literature accessed through databases such as PubMed and Google Scholar. Eligible sources comprised official regulations, guidance documents, policy reports, and peer-reviewed articles specifically addressing pharmaceutical e-labelling, while draft policies and unrelated documents were excluded. Data were synthesized using qualitative thematic analysis, and cross-jurisdictional comparisons were structured across predefined domains including regulatory scope, legal status, implementation stage, digital infrastructure, and stakeholder accessibility.
    KEY FINDINGS: Common challenges include maintaining authenticity, readability, and interoperability of e-labels. Technologies like QR codes, barcoding, and decision support tools increase safety and access. However, digital implementation and regulatory maturity differ generally between the developed and developing nations.
    Keywords:  Digitization; E-labelling; Electronic product information; Health care professionals.; Regulatory authority
    DOI:  https://doi.org/10.1007/s43441-026-00923-1
  42. Curr Pharm Des. 2026 Mar 11.
    Strategic Integration of Electronic Quality Management Systems with Quality Risk Management: Advancing Pharmaceutical Compliance and Operational Excellence.
    Shikha Baghel Chauhan, Indu Singh, Radhakrishan Gaur, Chirag Jain.
      The pharmaceutical sector requires strong and flexible quality systems to achieve operational excellence and regulatory compliance. Integrating Quality Risk Management (QRM) frameworks with Electronic Quality Management Systems (EQMS) provides a transformative approach to quality management across the pharmaceutical value chain. This paper investigates how EQMS and QRM can work together to promote proactive compliance, reduce process variability, and foster a culture of continuous improvement. While QRM offers a systematic process for identifying, evaluating, and managing quality risks throughout the product lifecycle, EQMS technologies provide real-time data collection, optimized documentation, automated workflows, and streamlined regulatory reporting. The integration of these systems enhances risk-based decision- making by addressing deviations, non-conformances, and change controls through analytics, trend analysis, and predictive modeling. Current industry practices, regulatory requirements from organizations such as the FDA and EMA, and technological developments that facilitate this integration, such as cloud-based EQMS systems and AI-enabled risk assessment tools, are critically assessed in this article. To demonstrate how integrated systems have facilitated faster time-to-market, reduced compliance gaps, and improved audit readiness, case studies and implementation models are examined. Additional considerations include system validation, user acceptance, and data integrity. Ultimately, EQMS and QRM integration represents a shift from reactive to proactive quality management, in line with ICH Q9 and ICH Q10 principles, positioning pharmaceutical firms to succeed in an increasingly complex and competitive regulatory environment. For stakeholders aiming to enhance quality outcomes through risk-based governance and digital transformation, this evaluation provides a strategic framework.
    Keywords:  ICH Q9.; Pharmaceutical compliance; cloud-based quality systems; data integrity; regulatory affairs
    DOI:  https://doi.org/10.2174/0113816128430008251210175444
  43. Cureus. 2026 Feb;18(2): e103667
    Successful Use of Chimeric Antigen Receptor T-cell (CAR-T) Therapy With Lisocabtagene Maraleucel in a Renal Transplant Recipient With Refractory/Relapsed Diffuse Large B-Cell Lymphoma (DLBCL).
    Waqqas Tai, Fatima Chaudhry, Nesreen Shahrour, Jessica Thomas, Afoma Anyadibe, Anuoluwa Oyetoran, Swathi Gopishetty, Precious Idogun, Dilip Samarapungavan, Jassim H Sarmad, Ishmael Jaiyesimi.
      This case describes a 53-year-old male with end-stage renal disease who developed monomorphic post-transplant lymphoproliferative disorder (PTLD) in the form of diffuse large B-cell lymphoma (DLBCL) after kidney transplantation. Despite initial treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), the patient's disease progressed, and he was referred for chimeric antigen receptor (CAR) T-cell therapy with lisocabtagene maraleucel (liso-cel). Given his post-transplant status, his immunosuppressive agents (tacrolimus and mycophenolate) were held, and prednisone was tapered to 5 mg daily to maintain minimal baseline immunosuppression. After lymphodepleting chemotherapy and liso-cel infusion, the patient experienced no significant toxicities, including cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). This case underscores the potential of CAR-T therapy for refractory/relapsed DLBCL in post-transplant patients, emphasizing the need for careful immunosuppressive management to balance graft protection and treatment efficacy.
    Keywords:  car-t cells in hematological malignancies; diffuse large b cell lymphoma (dlbcl); kidney transplant; liso-cel; lymphoma; post-transplant lymphoproliferative disorders
    DOI:  https://doi.org/10.7759/cureus.103667
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