bims-carter Biomed News
on CAR-T Therapies
Issue of 2026–04–12
forty-one papers selected by
Luca Bolliger, lxBio
  1. Chimeric antigen receptor T-cell therapy in pediatric neurological autoimmune diseases: mechanisms, clinical applications, and future perspectives.
  2. Advancements and expanding applications of CAR-T cell therapy.
  3. In vivo CAR-T cell therapy: latest updates from 2025 ASH annual meeting.
  4. From T cells to NK cells and macrophages: progress and challenges in CAR-based therapies and the involved gene delivery systems.
  5. Potential of CAR-T cell immunotherapy in rheumatoid arthritis.
  6. CAR-NK cell therapy for overcoming antigen heterogeneity and immunosuppressive tumor microenvironments.
  7. DROP-CARs: Engineering Reversible, Drug-Controlled CAR T Cell Activity with a Clinically Approved Small Molecule.
  8. Crosstalk between cytokines and tryptophan metabolism: Therapeutic potential for immune effector cell-associated neurotoxicity syndrome.
  9. Plying potency assays for immunotherapy of solid tumors.
  10. WC1-mediated co-stimulation in γδ T cells: Insights from ruminants and perspectives for human immunotherapy.
  11. Potential of chimeric antigen receptor (CAR) T cell immunotherapy in systemic lupus erythematosus (SLE).
  12. Q&A: Renier Brentjens on Obstacles and Opportunities in CAR T-cell Therapy.
  13. CAR T-cell therapy induced pseudoprogression.
  14. One woman, three autoimmune diseases: CAR-T therapy vanquishes ultra-rare disease trio.
  15. Shaping national networks to improve patient access to advanced therapy medicinal products in Europe.
  16. Patient experience data in regulatory and health technology assessment.
  17. CAR T-cell therapy "Living drugs" in systemic lupus erythematosus.
  18. Balancing the efficacy and safety of chimeric antigen receptor T-cell therapy by affinity combination.
  19. CAR T-cells in hematologic malignancies: Advances, challenges, and future directions.
  20. Potential of Chimeric Antigen Receptor-Engineered Mesenchymal Stem Cell (CAR-MSC) Therapy in the Treatment of Pre-Eclampsia.
  21. CAR-T therapy: Trailblazing CAR(ing) in cancer treatment.
  22. Chimeric antigen receptor macrophage (CAR-M) immunotherapy in autoimmune inflammatory rheumatic diseases.
  23. Epigenetic, epitranscriptomic, and metabolic control of T cell exhaustion.
  24. The emerging role of T cells in depression.
  25. Prediction models for CAR-T Cell therapy-related adverse events in hematologic malignancies: a systematic review and meta-analysis.
  26. NK cell adoptive transfer in acute myeloid leukemia: a systematic review and meta-analysis.
  27. Artificial Intelligence in Clinical Oncology: Multimodal Integration and Translational Development.
  28. Anonymization, accountability, and access: legal dimensions of health data sharing in federated networks. Perspectives from empirical study.
  29. Haem from stressed mitochondria can drive T cell exhaustion.
  30. CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome.
  31. Anti-CD52 therapy of rheumatic diseases: Revisited in the era of immune reset.
  32. Blockchain Applications in Core Healthcare Services: Patient Data, Research, and Institutional Processes.
  33. Deploying the common European manufacturing data space: The UNDERPIN and SM4RTENANCE frameworks' perspective.
  34. Cytokine armored CAR T cells for cancer immunotherapy.
  35. CAR-T cell therapy in breast cancer management: expanding horizon and overcoming challenges beyond hematologic cancers.
  36. Regulatory T cells as a potential treatment for autoimmune inflammatory rheumatic and musculoskeletal diseases.
  37. The rise of spatial TCR profiling: Emerging technologies and open challenges.
  38. 'Most Favored Nation' Drug Pricing: An Idea To What End?
  39. The use of complex clinical trials: a regulatory review.
  40. Impaired hematopoiesis affects apheresis and CAR T-cell product composition and treatment response.
  41. Malignancy and rheumatic diseases.
  1. Front Pediatr. 2026 ;14 1740566
    Chimeric antigen receptor T-cell therapy in pediatric neurological autoimmune diseases: mechanisms, clinical applications, and future perspectives.
    Weihao Ling, Chen Xu, Jihong Tang, Shifeng Lu, Chunfeng Wu.
      Pediatric neurological autoimmune diseases (PNADs) are a result of immune system abnormalities that target the central and peripheral nervous systems, leading to various neurological dysfunctions in children. The limitations of current immunotherapies underscore the necessity for more efficacious treatment interventions. The objective of this review is to examine the fundamental principles, recent advancements, and clinical applications of chimeric antigen receptor (CAR) T cell therapy in the treatment of pediatric neurological autoimmune diseases (PNADs). By specifically targeting and reducing pathogenic B cells, CAR-T therapy has the potential to reset the immune system. Growing evidence from preclinical animal studies, case reports, and early clinical trials suggests that CAR-T cell therapy has therapeutic potential in managing autoimmune diseases such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and systemic lupus erythematosus (SLE). However, several challenges remain, including the high cost of treatment, safety concerns such as cytokine release syndrome and neurotoxicity, and a lack of long-term safety data in pediatric populations. Future research should prioritize optimizing the management and evaluation model for the entire process, as well as refining CAR design and development, to enhance the safe and effective clinical application of CAR T-cell therapy in patients with PNADs.
    Keywords:  CAR-T cell therapy; autoimmune diseases; challenges; clinical application; pediatric neurological autoimmune diseases
    DOI:  https://doi.org/10.3389/fped.2026.1740566
  2. Front Immunol. 2026 ;17 1802718
    Advancements and expanding applications of CAR-T cell therapy.
    Xiang Zhang, Zi-Chang Liu, Ling-Jie Luo, Yan-Wei Wu, Xin-Gang Cui, Liang Chen.
      CAR T-cell therapy has become a transformative modality in oncology, demonstrating sustained clinical efficacy in hematologic malignancies. Recent investigations have expanded its potential beyond cancer to immune-mediated disorders, including autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus, as well as chronic viral infections including HIV and hepatitis B. This review examines the mechanistic foundations of CAR-T cells, advances in universal and allogeneic engineering strategies designed to mitigate graft-versus-host disease and host rejection, and emerging in vivo gene-delivery platforms that aim to bypass conventional ex vivo manufacturing. We further evaluate safety-control architectures, including logic-gated and inducible systems, and discuss translational barriers related to scalability, manufacturing standardization, and long-term immune durability. While technological innovations in genome editing, synthetic biology, and computational design continue to refine CAR-T platforms, substantial biological and logistical challenges remain. A critical synthesis of these evolving strategies is necessary to distinguish incremental optimization from paradigm-shifting advances and to define the future trajectory of CAR-based immunotherapy across oncology and immune-mediated diseases.
    Keywords:  CAR-T cell therapy; autoimmune diseases; gene editing; infectious diseases; universal CAR-T cells
    DOI:  https://doi.org/10.3389/fimmu.2026.1802718
  3. J Hematol Oncol. 2026 Apr 09. pii: 21. [Epub ahead of print]19(1):
    In vivo CAR-T cell therapy: latest updates from 2025 ASH annual meeting.
    Pan Gao, Jun Liu, Jun Ma, Hengrui Ma, Ya Zhang.
      Chimeric antigen receptor (CAR)-T cell therapy has demonstrated remarkable efficacy in treating hematological malignancies. However, this approach faces substantial limitations, including protracted manufacturing periods, elevated costs, restricted patient eligibility attributable to manufacturing constraints, and intolerate lymphodepleting preconditioning regimens. To address these challenges, in vivo CAR-T cell therapy has emerged as a promising alternative, directly engineering immune cells within the patient through targeted delivery systems such as engineered viral vectors, lipid nanoparticles, and other non-viral platforms. This approach offers immediate administration and enhanced scalability compared with ex vivo methods. The 2025 American Society of Hematology annual meeting presented multiple abstracts advancing this field, with this review focusing on studies demonstrating novel delivery system innovations, including engineered lentiviral vectors and non-viral platforms, as well as expanded therapeutic applications beyond oncology to autoimmune diseases. By integrating these conference presentations with recent peer-reviewed literature, this paper summarizes the current landscapes of in vivo CAR-T cell therapy presented at the conference.
    Keywords:  Delivery systems; Hematologic malignancies; In vivo CAR-T cell therapy; The 2025 ASH annual meeting; Therapeutic applications
    DOI:  https://doi.org/10.1186/s13045-026-01787-6
  4. Int J Pharm. 2026 Apr 03. pii: S0378-5173(26)00296-6. [Epub ahead of print]696 126848
    From T cells to NK cells and macrophages: progress and challenges in CAR-based therapies and the involved gene delivery systems.
    Margarida C Guerreiro, Inês S Pinto, Dina Farinha, Henrique Faneca.
      Chimeric antigen receptor (CAR)-based therapies have transformed the treatment of hematological malignancies, with CAR-T cell therapies establishing themselves as effective clinical options. Building on this success, recent research has expanded CAR engineering to natural killer (CAR-NK) cells and macrophages (CAR-M), aiming to address key limitations such as manufacturing complexity, safety concerns, and suboptimal efficacy against solid tumors. Advances in non-viral gene delivery systems have further progressed the field, providing alternatives to traditional viral vectors by enabling efficient, scalable, and less toxic CAR gene transfer. This review summarizes the evolution and latest developments in CAR-T, CAR-NK, and CAR-M therapies, with a focus on innovative non-viral delivery platforms. We highlight current clinical achievements, ongoing challenges, and the convergence of cell engineering and delivery approaches that are broadening the therapeutic potential of CAR technology. Continued progress in these areas can make personalized, targeted cancer immunotherapies more accessible, versatile, and beneficial for a wider patient population.
    Keywords:  Chimeric antigen receptor therapy; Gene delivery systems; Immunotherapy; Macrophages; Natural killer cells; T-lymphocytes
    DOI:  https://doi.org/10.1016/j.ijpharm.2026.126848
  5. Clin Rheumatol. 2026 Apr 08.
    Potential of CAR-T cell immunotherapy in rheumatoid arthritis.
    Ian C Chikanza, Lazaros I Sakkas.
      Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Despite the availability of various treatment options, many patients remain refractory to conventional therapies. Recent advancements in cellular immunotherapy, particularly chimeric antigen receptor T-cell (CAR-T cell) therapy, have demonstrated promising potential in targeting the underlying immunological mechanisms of RA. This paper explores the rationale for CAR-T cell therapy in RA, the mechanisms by which CAR-T cells may exert therapeutic effects, the current state of clinical research, and the challenges that need to be addressed for the successful implementation of CAR-T cell immunotherapy in RA treatment. We also discuss future directions for improving the safety and efficacy of CAR-T cell therapy in autoimmune diseases.
    Keywords:  B cells; CAR-T cells; Immunotherapy; Rheumatoid arthritis; T cells
    DOI:  https://doi.org/10.1007/s10067-026-08095-x
  6. Hum Immunol. 2026 Apr 07. pii: S0198-8859(26)00074-1. [Epub ahead of print]87(6): 111728
    CAR-NK cell therapy for overcoming antigen heterogeneity and immunosuppressive tumor microenvironments.
    Mohammad Qutub, Tanvi Premchandani, Sakshi Bhagat, Amol Tatode, Jayshree Taksande, Milind Umekar, Ujban Md Hussain, Rahmuddin Khan.
      Chimeric antigen receptor engineered natural killer cells (CAR-NK) have emerged as a transformative strategy in cancer immunotherapy, offering MHC-independent cytotoxicity, reduced graft-versus-host disease risks, and allogeneic "off-the-shelf" applicability. This review synthesizes advancements in CAR-NK design, including fourth-generation "armored" constructs with cytokine secretion, metabolic reprogramming via mTOR/c-Myc modulation, and CRISPR-mediated knockout of inhibitory checkpoints (CISH). Clinical trials demonstrate efficacy in hematologic and solid tumors, with HER2-, B7-H3-, and NKG2D-targeted CAR-NK cells showing manageable toxicity and minimal cytokine release syndrome. Innovations such as non-viral gene delivery (Sleeping Beauty transposon, mRNA electroporation) and combinatorial approaches (immune checkpoint inhibitors, chemokine receptor integration) enhance tumor infiltration and persistence. Despite progress, challenges persist, including tumor heterogeneity, immunosuppressive tumor microenvironment barriers, and scalability of manufacturing protocols. This review critically evaluates preclinical and clinical data, highlighting emerging targets (EpCAM, CEA), engineering paradigms (logic-gated CARs, trogocytosis-mediated transfer), and strategies to counteract antigen loss and metabolic stress. By addressing knowledge gaps in TME modulation and standardizing clinical protocols, this work aims to catalyze interdisciplinary efforts to advance safer, durable CAR-NK therapies for refractory cancers.
    Keywords:  Antigen heterogeneity; CAR-NK cell therapy; Cancer immunotherapy; Clinical translation; Metabolic reprogramming; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.humimm.2026.111728
  7. Cancer Res. 2026 Apr 06.
    DROP-CARs: Engineering Reversible, Drug-Controlled CAR T Cell Activity with a Clinically Approved Small Molecule.
    Adam J Stevens, Wendell A Lim.
      A major limitation in applying chimeric antigen receptor (CAR) T cells to solid tumors is toxicity in healthy tissues caused by a lack of tumor-specific targets. A promising strategy to overcome this deleterious cytotoxicity is to engineer control into CAR T cells beyond that conferred by antigen recognition alone. In a recent issue of Nature Chemical Biology, Scheller and colleagues report the development of a CAR that is inactivated through introducing the small molecule, venetoclax, which is a clinically approved targeted Bcl-2 inhibitor. The authors design venetoclax-dependent release of the CAR extracellular binding domain, thereby disrupting T cell contact with tumor cells and suppressing cytotoxicity. Furthermore, they demonstrate the reversibility of this approach, as withdrawal of the drug restores CAR T cell function. This work establishes a foundation for clinically translatable remote-controlled CAR T cell therapy for solid tumors.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-26-1348
  8. Biochem Pharmacol. 2026 Apr 07. pii: S0006-2952(26)00282-0. [Epub ahead of print] 117949
    Crosstalk between cytokines and tryptophan metabolism: Therapeutic potential for immune effector cell-associated neurotoxicity syndrome.
    Jianghua Wu, Dehu Li, Heng Mei, Yu Hu.
      Neuromodulation by cytokine networks plays a pivotal role in maintaining central nervous system (CNS) homeostasis. Cytokine release syndrome (CRS) and neurotoxicity are frequently and concurrently observed during chimeric antigen receptor (CAR) T cell therapy, suggesting that they are intrinsically related. Immune hyperactivation occurs after CAR-T cell infusion into human body, and the excessive secretion of cytokines results in an "overspill" into the circulation, causing multiple pathophysiological disorders, such as systemic inflammation, elevated vascular permeability and metabolic disturbance. Mounting evidence has revealed that the various pathologies of CNS are accompanied by the alterations in tryptophan metabolism. Here, we will review the advances in immune effector cell-associated neurotoxicity syndrome (ICANS) during CAR-T cell therapy, with particular focus on the crosstalk between cytokines and tryptophan metabolism for the implications for ICANS. Based on the role of tryptophan metabolism in neurological disorders, we propose a model wherein acute inflammation combines to increase brain permeability, and cytokines driven-tryptophan metabolism may subsequently synergize with host cells to trigger the occurrence of ICANS. Furthermore, we discuss the potential of crosstalk between cytokines and tryptophan metabolism as therapeutic targets in clinical applications to provide insight into possible therapeutic strategies for ICANS.
    Keywords:  CAR-T cell; Cytokines; ICANS; Tryptophan metabolism
    DOI:  https://doi.org/10.1016/j.bcp.2026.117949
  9. Front Immunol. 2026 ;17 1770222
    Plying potency assays for immunotherapy of solid tumors.
    Jorge S Burns, Riana Gjeta, Petr Lesný, Joaquim Vives.
      Potency assays for cellular immunotherapies have advanced considerably yet remain only partially aligned with the complex requirements of solid tumors, where trafficking, persistence, metabolic fitness and spatially constrained effector function are key determinants of in vivo performance. Critical quality attributes and mechanism of action can be used to anchor more informative potency strategies for tumor-infiltrating lymphocytes and CAR-engineered platforms, including CAR T, CAR-NK, CAR-M and CAR-γδ T cells. Emerging three-dimensional models, spatial biology, label-free real-time technologies and AI-enabled analytics are examined as routes to integrate microenvironmental stressors and dynamic single-cell behavior into assay design. A "plying" framework is proposed to organize potency assessment into layered, iteratively refined panels that span lean, regulatory compliant release testing through to comprehensive exploratory profiling, providing a practical path toward clinically relevant and regulatorily acceptable potency assurance for solid tumor immunotherapy products.
    Keywords:  3D tumor culture models; CAR T-cell therapy; CAR-engineered immune cell platforms; artificial intelligence; axicabtagene ciloleucel; potency assays; regulatory frameworks for advanced therapies; spatial biology
    DOI:  https://doi.org/10.3389/fimmu.2026.1770222
  10. Int Rev Immunol. 2026 Apr 06. 1-18
    WC1-mediated co-stimulation in γδ T cells: Insights from ruminants and perspectives for human immunotherapy.
    Rümeysa Berra Karataş, Furkan Ayaz, Esra Aydemir.
      Gamma-delta (γδ) T cells, which bridge innate and adaptive immunity, are attractive candidates for immunotherapy. Significant interspecies differences exist, particularly between humans and ruminants. In ruminants, γδ T cells are a major circulating population characterized by the Workshop Cluster 1 (WC1) family, a unique set of Scavenger Receptor Cysteine-Rich (SRCR) co-receptors. WC1 molecules function dually as pattern recognition receptors (PRRs) and essential co-stimulators for the γδ T cell receptor (TCR). Specific WC1 isoforms (e.g. WC1.1+, WC1.2+) are associated with distinct functional predispositions, within a broader functional plasticity observed in both human and murine γδ T cell subsets. This review compares human and ruminant γδ T cell biology, proposing the WC1 co-stimulatory system as a functional paradigm for next-generation human T cell therapies. "WC1-inspired" synthetic receptors could provide more physiological, sustained activation, potentially overcoming key therapeutic limitations such as antigen escape and severe toxicity. Despite translational challenges, including the lack of a direct human WC1 ortholog, the ruminant model provides a critical potential for designing more durable and context-responsive immunotherapies.
    Keywords:  CAR-T cells; T-cell receptor (TCR); WC1 (Workshop Cluster 1); ruminants; ımmunotherapy; γδ T cells (gamma-delta T cells)
    DOI:  https://doi.org/10.1080/08830185.2026.2650138
  11. Clin Rheumatol. 2026 Apr 07.
    Potential of chimeric antigen receptor (CAR) T cell immunotherapy in systemic lupus erythematosus (SLE).
    Ian C Chikanza, Christina Katsiari, Lazaros I Sakkas.
      Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease characterized by multiorgan inflammation due to the dysregulation of the immune system. Despite the availability of conventional immunosuppressive therapies, the management of SLE remains challenging due to treatment resistance and significant side effects. Recent advancements in immunotherapy, particularly chimeric antigen receptor (CAR) T-cell therapy, have shown potential as a novel treatment for autoimmune diseases, including SLE. As of 2025, the treatment landscape for systemic lupus erythematosus (SLE) is undergoing a significant transformation, driven by innovative therapies aiming to provide more effective and potentially curative options for patients. This review provides an overview of the current research on CAR T-cell therapy in SLE, discusses the mechanisms underlying its efficacy, and explores the potential challenges and future directions of this promising therapeutic approach.
    Keywords:  BCMA; Biodrug; Biologic; CAR T Cells; CD19/BCMA; CD22; CD40L; CD9; RA; SLE; Systemic lupus erythematosus
    DOI:  https://doi.org/10.1007/s10067-026-08100-3
  12. Cancer Discov. 2026 Apr 10. OF1
    Q&A: Renier Brentjens on Obstacles and Opportunities in CAR T-cell Therapy.
       ABSTRACT: Renier Brentjens, MD, PhD, a pioneer of chimeric antigen receptor (CAR) T-cell therapy, speaks about his early work in the field, the current limitations of CAR T cells, and how researchers might advance the technology in the coming years.
    DOI:  https://doi.org/10.1158/2159-8290.CD-NW2026-0032
  13. Front Immunol. 2026 ;17 1691562
    CAR T-cell therapy induced pseudoprogression.
    Erin A Dean.
      Pseudoprogression is defined as a seeming post-therapy increase in tumor burden on imaging that recedes on subsequent reimaging without additional therapy. The origins of pseudoprogression lie in the field of immunology with current understanding of the imaging finding coming mostly from experience with checkpoint inhibitors used for management of solid tumors. With the wider administration of chimeric antigen receptor (CAR) T-cell therapy for the treatment of hematologic malignancies, CAR T-cell induced pseudoprogression (CARTiPP) has also been noted although it has remained an underreported, although likely rare, adverse event lacking clear description and management guidelines. CARTiPP can obscure response assessment in patients and lead to serious clinical complications due to edema-driven compression of organs or tissue. This mini review summarizes the emergence of pseudoprogression with the rise of immunotherapy along with the modifications of radiologic guidelines for correct interpretation of scans as a key non-invasive technique for overcoming the associated diagnostic challenges. It discusses the limited available data on the nature of CARTiPP in the setting of the tumor microenvironment and its meaning for the care of patients receiving CAR T-cell therapy.
    Keywords:  CAR T-cell therapy; CARTiPP; PET/CT scan; checkpoint inhibitors; hematologic malignancies; pseudoprogression; solid tumors; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2026.1691562
  14. Nature. 2026 Apr 09.
    One woman, three autoimmune diseases: CAR-T therapy vanquishes ultra-rare disease trio.
    Edward Chen.
      
    Keywords:  Immunology; Medical research
    DOI:  https://doi.org/10.1038/d41586-026-01108-4
  15. Drug Discov Today. 2026 Apr 03. pii: S1359-6446(26)00066-8. [Epub ahead of print] 104661
    Shaping national networks to improve patient access to advanced therapy medicinal products in Europe.
    RSNN SIG Advanced Therapies Steering Committee
      Advanced therapy medicinal products (ATMPs) offer the potential to address unmet medical needs, yet ensuring sustainable patient access remains challenging. In response, national ATMP networks are being established across Europe to strengthen ATMP development, cooperation between stakeholders and patient access. This targeted review provides an overview of (emerging) national ATMP networks across Europe and reflects on learnings and best practices. Drawing on insights from a Dutch multistakeholder workshop, a targeted European survey and interviews with established networks in the UK, Sweden and Ireland, this review concludes with recommendations to support the establishment of ATMP networks and improve patient access to ATMPs.
    DOI:  https://doi.org/10.1016/j.drudis.2026.104661
  16. Qual Life Res. 2026 Apr 10. pii: 130. [Epub ahead of print]35(5):
    Patient experience data in regulatory and health technology assessment.
    Jessica Roydhouse, Wen-Hung Chen, Lori McLeod, Brittany Lapin.
      
    DOI:  https://doi.org/10.1007/s11136-026-04237-5
  17. Best Pract Res Clin Rheumatol. 2026 Apr 08. pii: S1521-6942(26)00026-4. [Epub ahead of print] 102141
    CAR T-cell therapy "Living drugs" in systemic lupus erythematosus.
    Leila Khalili, Alberto Nordmann-Gomes, Marta Mosca, Anca Askanase.
       INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative therapeutic option for patients with severe, refractory autoimmune conditions. Since 2022, several authors have published their experience using CAR T-cell therapy for patients with systemic lupus erythematosus (SLE).
    METHODS: This narrative review summarizes the biological rationale, diverse modalities, targets and platforms, the emerging clinical efficacy and safety data, as well as the barriers and innovations regarding the use of CAR T-cell therapy in SLE.
    RESULTS: Among the 16 studies reviewed, 13 evaluated products targeting CD19 and the remaining three bispecific products targeting CD19 and B-cell maturation antigen (BCMA). Twelve studies assessed autologous therapies and four allogeneic products. Therapies evaluating CAR natural killer cells (CAR-NK), gamma delta T-cells (γδ T-cells), other transduction methods, and even in vivo CARs are currently being evaluated. Early data has demonstrated significant clinical efficacy, including rapid disease activity reductions, drug-free remission in over 80%, achievement of low-level disease activity in almost 90%, and remission in 70% of the patients where these outcomes were assessed. Cytokine release syndrome occurred in 56% of the patients evaluated, almost exclusively being grade 1 or 2 events, and neurotoxicity was rare.
    CONCLUSIONS: CAR T-cell therapy has demonstrated encouraging clinical efficacy and reassuring safety outcomes so far. However, longer prospective studies are needed to assess durability of response, long term safety, factors associated with poor response, and the appropriate selection and timing of patients for therapy.
    Keywords:  CAR T-cell therapy; Cellular therapy; Chimeric antigen receptor; Systemic lupus erythematosus
    DOI:  https://doi.org/10.1016/j.berh.2026.102141
  18. Nat Commun. 2026 Apr 10. pii: 3413. [Epub ahead of print]17(1):
    Balancing the efficacy and safety of chimeric antigen receptor T-cell therapy by affinity combination.
    Linda Warmuth, Sarah Dötsch, Manuel Trebo, Sarah Bellucci, Sophia Engels, Rafael Valdivia Manrique, Karl Moukarzel, Julius M Schütz, Monika Hammel, Adrian Straub, Sabrina Wagner, Anna Hochholzer, Ciro Salinno, Jacqueline Seigner, Charlotte U Zajc, Georg P Schmidt, Josefine Michael, Thomas Nerreter, Michael Hudecek, Michael W Traxlmayr, Monica Casucci, Stanley R Riddell, Mateusz P Poltorak, Dirk H Busch, Elvira D'Ippolito.
      Recent studies suggest that Chimeric Antigen Receptor (CAR) binding affinity to its ligand affects CAR-T-cell functionality. Affinity engineering towards lower binding strengths might mitigate therapeutic side effects arising from intense CAR-T-cell activation as well as tumor relapse due to antigen-escape or limited persistence of CAR-T cells during sustained activation via high-affinity receptors. Here we characterize a broad range of CARs with varying affinities to the same target epitope and leverage the insights we gain to design a combined high- and low-affinity CAR product. While CAR affinity impacts in vitro functionality minimally, it strongly correlates with tumor control in vivo. Low-affinity binders cause only mild cytokine release syndrome (CRS) in humanized mouse models at the expense of anti-tumour efficiency. In mixtures with low-affinity CARs, high-affinity CARs maintain strong functionality while showing reduced signs of exhaustion and monocyte-induced cytokine production, compared to high-affinity CAR-T cells alone. In long term in vitro and in vivo settings, low-affinity CAR-T cells dominate over time, proving more resilience to chronic antigen exposure. Overall, our findings demonstrate that affinity combination represents a promising strategy to generate more effective CAR-T-cell products with an improved therapeutic index, beyond affinity engineering alone.
    DOI:  https://doi.org/10.1038/s41467-026-71354-7
  19. iScience. 2026 Apr 17. 29(4): 115213
    CAR T-cells in hematologic malignancies: Advances, challenges, and future directions.
    Karol J Hernández-Idarraga, Andrea J Arias-Rozo, Martha L Arango-Rodríguez, Claudia L Sossa, Silvia M Becerra-Bayona.
      Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of hematologic malignancies, achieving high remission rates in relapsed or refractory B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma. By redirecting autologous or allogeneic T lymphocytes against tumor-associated antigens such as CD19 and TNFRSF17, CAR T-cells overcome resistance to conventional therapies. Progressive optimization of CAR design-from early constructs to armored and logic-gated platforms-has enhanced persistence, specificity, and safety. Pivotal trials and real-world evidence confirm durable responses, although challenges remain, including cytokine release syndrome, neurotoxicity, manufacturing complexity, high cost, and limited global access. Emerging strategies, such as multi-antigen targeting, gene editing technologies, and in vivo CAR delivery, aim to improve efficacy and scalability. Integration of artificial intelligence and point-of-care manufacturing may further streamline production and patient selection. Continued innovation will determine the long-term impact of CAR T-cell therapy as a scalable pillar of precision hematologic oncology.
    Keywords:  oncology; therapeutics
    DOI:  https://doi.org/10.1016/j.isci.2026.115213
  20. Am J Reprod Immunol. 2026 Apr;95(4): e70236
    Potential of Chimeric Antigen Receptor-Engineered Mesenchymal Stem Cell (CAR-MSC) Therapy in the Treatment of Pre-Eclampsia.
    Yixiao Wang, Huan Huang, Ruizhe Jia.
       BACKGROUND: Chimeric antigen receptor (CAR) is a receptor engineered to engraft defined specificity onto immune effector cells, usually T cells, and enhance cellular function. Currently, the anticancer effects of CAR-engineered T cells, macrophages, and NK cells are being intensively explored. Pre-eclampsia (PE) is a pregnancy-specific disease with complex pathogenesis, and no effective treatment exists other than delivery. Placental dysfunction is a major contributing factor; the abnormal placenta releases factors into the maternal bloodstream, leading to systemic inflammation and widespread endothelial dysfunction.
    OBJECTIVE: This review comprehensively assesses the therapeutic prospects of CAR-engineered mesenchymal stem cell (CAR-MSC) therapies in addressing the pathophysiological mechanisms of PE, while outlining future directions for CAR-MSC integrated treatment strategies.
    CONCLUSION AND PROSPECTS: Although non-tumor research based on CAR technology is still in its early stages, in-depth investigation into CAR-MSCs may offer novel insights and perspectives for the treatment of PE by modulating placental immune function and enhancing placental repair. Given that pregnant women constitute a special population, safety considerations must be fully prioritized in future research.
    Keywords:  chimeric antigen receptor; mesenchymal stem cell; pre‐eclampsia
    DOI:  https://doi.org/10.1111/aji.70236
  21. Oncotarget. 2026 Jan 06. 17(1): 54-56
    CAR-T therapy: Trailblazing CAR(ing) in cancer treatment.
    Uzma Saqib, Monika Pandey, Krishnan Hajela.
      
    Keywords:  CAR-T therapy; cancer; therapeutic approaches
    DOI:  https://doi.org/10.18632/oncotarget.28836
  22. Clin Rheumatol. 2026 Apr 08.
    Chimeric antigen receptor macrophage (CAR-M) immunotherapy in autoimmune inflammatory rheumatic diseases.
    Ian C Chikanza, Lazaros I Sakkas.
      Chronic autoimmune inflammatory rheumatic diseases (AIRD), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis, systemic sclerosis (SSc), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), are characterized by the dysregulation of the immune system and that of the neuroendocrine immune networks, leading to chronic inflammation and tissue damage. Perturbations of T, B, and macrophage cells result in uncontrolled inflammation. Traditional therapeutic approaches have focused on immunosuppressive drugs but more recently the use of biologics targeting specific cytokines or receptors on immune cells, and intracellular JAK pathways has been employed. However, these therapies often have limited efficacy and significant side effects. Moreover, they are not globally accessible due to high drug costs especially in poor as well as low- to middle-income countries. Cell immunotherapy, such as CAR-T and CAR-M cell therapy based on chimeric antigen receptor (CAR) technology, is opening up novel potential avenues for a precision approach to managing AIRD. This area is still experimental and in the research phase. This paper reviews the potential of CAR-M immunotherapy in AIRDs, highlighting its mechanisms of action and therapeutic applications.
    Keywords:  Ankylosing spondylitis (AS); Autoimmune rheumatic disease; CAR-M cells; CAR-T cells; Cell immunotherapy; Chimeric antigen receptor (CAR) technology; Juvenile idiopathic arthritis (JIA); Rheumatoid arthritis (RA); Systemic lupus erythematosus (SLE); Systemic sclerosis
    DOI:  https://doi.org/10.1007/s10067-026-08101-2
  23. Trends Cancer. 2026 Apr 09. pii: S2405-8033(26)00057-9. [Epub ahead of print]
    Epigenetic, epitranscriptomic, and metabolic control of T cell exhaustion.
    Chloe Slater, Albane Simon, Marguerite Laprie-Sentenac, Laurie Menger.
      T cell exhaustion is an adaptive dysfunctional state driven by chronic antigen exposure and an immunosuppressive tumor microenvironment, which significantly impedes effective antitumor immunity and T cell therapies. This progressive loss of effector function and memory potential is governed by the complex and coordinated interplay of epigenetic, transcriptional, epitranscriptomic, and metabolic networks, which collectively establish stable exhaustion-associated programs. Emerging evidence demonstrates that modulating these layers, whether permanently or transiently, can reverse exhaustion and reinvigorate T cell function. Furthermore, core metabolites serve as shared cofactors, directly linking cellular metabolism to these epigenetic and epitranscriptomic changes. Characterizing these multilayered regulatory mechanisms is critical for developing novel strategies to reprogram exhausted T cells and improve therapeutic efficacy against cancer.
    Keywords:  CAR T cells; T cell exhaustion; T cell therapy; epigenetics; epitranscriptomics; metabolism
    DOI:  https://doi.org/10.1016/j.trecan.2026.03.002
  24. Front Psychiatry. 2026 ;17 1780383
    The emerging role of T cells in depression.
    Huaibing Wang, Hongxia Tao, Minlan Yuan, Wei Zhang.
      Depression is increasingly recognized as a disorder involving immune brain interactions beyond classical monoaminergic dysfunction. Among immune components, T cells have emerged as key regulators linking peripheral immune dysregulation to central neuroinflammation and impaired neuroplasticity. Accumulating clinical and preclinical evidence indicates that alterations in T cell subsets, including regulatory T cells, Th1 cells, and Th17 cells, contribute to depressive pathophysiology through coordinated effects on blood-brain barrier permeability, glial activation, cytokine signaling, and neurotrophic support. This review synthesizes current evidence on the mechanisms by which T cells migrate into the central nervous system and modulate depressive behaviors. Particular emphasis is placed on the T cell regulation of brain derived neurotrophic factor signaling, and a role for T cell derived extracellular vesicles as modulators of immune neural communication and neuroplasticity. Finally, we discuss the therapeutic implications of targeting T cells in depression, including modulation of T cell subset balance, cytokine-based interventions, microbiota immune regulation, and inhibition of pathogenic T cell trafficking into the brain. Together, these findings position T cells as central orchestrators of immune neural crosstalk and promising targets for mechanism informed immunotherapies in depression.
    Keywords:  T cells; depression; immunotherapy; neuroinflammation; neuroplasticity
    DOI:  https://doi.org/10.3389/fpsyt.2026.1780383
  25. BMC Cancer. 2026 Apr 06.
    Prediction models for CAR-T Cell therapy-related adverse events in hematologic malignancies: a systematic review and meta-analysis.
    Linrui Ye, Luqing Liao, Lulu Wang, Xuejian Zhao, Jitao Zeng, Xuehu Xu.
      
    Keywords:  Adverse events; Chimeric antigen receptor T-cell therapy; Hematologic malignancies; Meta-analysis; Prediction modeling; Systematic review
    DOI:  https://doi.org/10.1186/s12885-026-15877-8
  26. Front Immunol. 2026 ;17 1717413
    NK cell adoptive transfer in acute myeloid leukemia: a systematic review and meta-analysis.
    Letícia Dalla Vecchia Grassi, Gabriela de Toledo Passos Candelaria, Isabella de Oliveira Dias, Aline Raposo Nishimoto, Karina Fontão, Felipe Medauar Reis de Andrade Moreira, Heitor Duarte de Andrade, José Mauro Kutner, Nelson Hamerschlak, Juliana Aparecida Preto De Godoy, Leonardo Javier Arcuri, Lucila Nassif Kerbauy.
       Background: Acute myeloid leukemia (AML) remains associated with high relapse rates and poor long-term survival, particularly in refractory patients or those ineligible for hematopoietic stem cell transplantation (HSCT). Adoptive transfer of natural killer (NK) cells has emerged as a promising immunotherapeutic strategy due to intrinsic cytotoxicity, low risk of graft-versus-host disease (GVHD), immune restoration capacity, and feasibility of allogeneic off-the-shelf manufacturing.
    Methods: A systematic review of phase 1-2 clinical trials evaluating non-genetically modified NK-cell adoptive transfer was performed using PubMed and EMBASE (2000-2024). Study selection and data extraction were conducted independently by two reviewers in Rayyan®. Study characteristics, interventions, and outcomes were extracted. Response rate in relapsed/refractory (R/R) AML receiving NK monotherapy was pooled using single-proportion meta-analysis. One-year disease-free survival (DFS) in other settings was pooled by inverse variance using logarithm-transformed rates. Heterogeneity (I²), publication bias, and study quality (NIH before-after tool) were assessed.
    Results: Of 790 records identified, 29 studies were included, predominantly single-arm phase I/II trials (one randomized phase II). In R/R AML (11 studies; 217 patients), pooled response rate was 35% (95% CI 29-42; I²=30%), with 20.2% proceeding to HSCT. Higher responses were observed in strategies enhancing NK activation or persistence, including expanded multi-infusion platforms and CIML-NK. In low-/intermediate-risk AML in remission (3 studies; 38 patients), pooled 1-year DFS was 82% (95% CI 56-100; I²=0). In high-risk AML in remission and ineligible for HSCT (5 studies; 59 patients), pooled 1-year DFS was 26% (95% CI 12-55; I²=84). In studies combining NK transfer with haploidentical HSCT (9 studies; 303 patients), pooled 1-year DFS was 40% (95% CI 27-57; I²=94). Toxicities were generally mild, GVHD rates were low (0-8%), and severe events were uncommon. NK-cell persistence was typically short, improving with multiple infusions and CIML approaches.
    Conclusion: Adoptive allogeneic NK-cell transfer appears safe and clinically promising, particularly for patients unfit for intensive therapy or HSCT. At present, its use should remain limited to clinical trials. Future studies should define the optimal approach that maximizes clinical activity while maintaining low toxicity and achieving durable persistence of allogeneic NK cells.
    Keywords:  acute myeloid leukemia; cellular immunotherapy; efficacy; natural killer cells; safety
    DOI:  https://doi.org/10.3389/fimmu.2026.1717413
  27. Cancer Lett. 2026 Apr 08. pii: S0304-3835(26)00256-9. [Epub ahead of print] 218493
    Artificial Intelligence in Clinical Oncology: Multimodal Integration and Translational Development.
    Ruichong Lin, Zhenhui Zhao, Zhonghai Liu, Jing Kang, Kang Zhang, Xiaoying Huang, Yunfang Yu.
      Artificial intelligence (AI) is rapidly reshaping clinical oncology, as cancer care increasingly relies on integrating heterogeneous data streams spanning radiology, digital pathology, genomics, and longitudinal electronic health records. However, the sheer complexity and fragmentation of these multimodal inputs remain a major bottleneck for achieving truly personalized cancer management. Recent advances in AI, including foundation models, synthetic data generation, large language models, and agents, are enabling more robust representation learning, cross-modal reasoning, and clinically actionable decision support beyond what traditional single-modality systems can provide. AI-powered platforms are now accelerating molecular subtyping, refining risk stratification, and supporting individualized therapeutic recommendations by jointly modeling imaging, tissue architecture, and molecular landscapes. Moreover, emerging virtual cell and mechanistic foundation frameworks introduce a new computational paradigm for simulating cellular responses and drug-tumor interactions, offering predictive insights for treatment design and drug discovery. Despite these breakthroughs, critical challenges persist, including limited generalizability across patient populations and centers, insufficient prospective validation, regulatory uncertainty, scalability constraints, and ethical concerns surrounding fairness, transparency, and privacy. In this review, we synthesize the latest progress in multimodal oncology AI through a translational lens, emphasizing methodological trade-offs, validation readiness, and responsible deployment frameworks. We highlight how AI is moving from performance-driven benchmarking toward clinically trustworthy precision cancer care, with transformative implications for early detection, diagnosis, therapy optimization, drug development, and clinical trial design.
    Keywords:  Artificial Intelligence; Clinical Decision Support; Multimodal Data Integration; Oncology; Precision Medicine
    DOI:  https://doi.org/10.1016/j.canlet.2026.218493
  28. Front Digit Health. 2026 ;8 1719728
    Anonymization, accountability, and access: legal dimensions of health data sharing in federated networks. Perspectives from empirical study.
    Magdalena Kogut-Czarkowska, Mahsa Shabani.
      This paper explores the perspectives of stakeholders involved in federated networks for health data sharing, focusing on the legal and practical dimensions of data protection and governance under GDPR and EHDS in the development of such infrastructures. Using a qualitative approach centered on perspectives of 19 experts with experience in projects building federated networks, it investigates the perceived challenges in fulfilling specific obligations under the GDPR, as well as in establishing the contractual framework of a federated network, including the arrangements and mechanisms required to control data access and to define the conditions for lawful and effective data sharing and reuse. The study critically assesses the commonly cited assurance that "data never leaves the node" and evaluates the compatibility of federated approaches with data protection requirements. It highlights key tensions between legal theory and practical implementation, offering insights relevant to the design and governance of other federated architectures and emerging European data spaces. Study results indicate that while the advantages of a federated approach, such as data minimization, should not be discarded, there are also significant challenges of aligning federated networks architectures with data protection requirements in particular. Federated networks help initiate discussions about data sharing with new data holders, but they do not offer a straightforward solution to legal and technical challenges of data sharing.
    Keywords:  EHDS; GDPR; data protection; federated networks; health data; secondary use
    DOI:  https://doi.org/10.3389/fdgth.2026.1719728
  29. Nat Rev Immunol. 2026 Apr 07.
    Haem from stressed mitochondria can drive T cell exhaustion.
    Yvonne Bordon.
      
    DOI:  https://doi.org/10.1038/s41577-026-01301-6
  30. Med. 2026 Apr 09. pii: S2666-6340(26)00078-4. [Epub ahead of print] 101075
    CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome.
    Isabel K Korte, Soraya Kharboutli, Simon Völkl, Lisa Heberling, Julia K Scholz, Hella Pfeiffer, Julian Strobel, Thomas Harrer, Sascha Kretschmann, Ingrid Vasova, Armin Gerbitz, Susanne Achenbach, Bernd Spriewald, Stefan Krause, Kerstin Gutsche, Malte von Bonin, Christoph Röllig, Michael Aigner, Andreas Mackensen, Fabian Müller.
       BACKGROUND: Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and antiphospholipid antibody syndrome (APLAS) are B cell-driven autoimmune diseases defined by pathogenic autoantibodies. CD19-directed chimeric antigen receptor (CAR)-T cells have recently demonstrated the ability to reset dysregulated B cells and induce long-lasting remission in refractory systemic autoimmune diseases. Evidence for efficacy in severe, treatment-refractory AIHA, however, is limited.
    METHODS: We report the clinical course of a 47-year-old woman with life-threatening cold- and warm-agglutinin AIHA refractory to nine prior treatment lines, accompanied by ITP and APLAS. In an uncontrolled flare, she received a fludarabine/cyclophosphamide-containing lymphodepletion followed by autologous CD19-directed, 4-1BB-costimulated CAR-T cells (zorpocabtagene-autoleucel [Zorpo-cel], 1 × 106/kg) on the basis of compassionate use. Treatment efficacy and safety were assessed over an 11-month follow-up period.
    FINDINGS: Zorpo-cel showed a rapid and sustained B cell depletion. Transfusion independence was achieved by day 7, with hemoglobin normalization by day 25, including resolution of hemolysis markers. Cold-agglutinin titers decreased, and previously elevated antiphospholipid antibodies normalized without recurrence throughout 11 months of follow-up. ITP stabilized. No cytokine release syndrome or neurotoxicity occurred. Mild transaminase elevation and thrombocytopenia were observed, most likely correlating with pre-existing severe iron overload due to erythrocyte transfusions.
    CONCLUSION: This case demonstrates that CD19-directed CAR-T cell therapy can induce rapid, durable remission of severe, refractory cold-agglutinin AIHA and simultaneously improve coexisting APLAS and ITP on a favorable toxicity profile. However, more data from controlled clinical trials are needed for final conclusions.
    FUNDING: This work was funded by Deutsche Forschungsgemeinschaft and Deutsche Krebshilfe.
    Keywords:  4-1BB-costimulated CAR-T cells; AID; AIHA; APLAS; B cell depletion; B cell reset; CAR-T cells; ITP; Zorpo-cel; anti-CD19 CAR-T cell therapy; chimeric antigen receptor T cells; cold-agglutinin AIHA; hemolytic anemia; refractory AIHA; translation to patients
    DOI:  https://doi.org/10.1016/j.medj.2026.101075
  31. Autoimmun Rev. 2026 Apr 07. pii: S1568-9972(26)00070-4. [Epub ahead of print] 104056
    Anti-CD52 therapy of rheumatic diseases: Revisited in the era of immune reset.
    Fadi Hassan, John D Isaacs, Mohammad E Naffaa.
      Alemtuzumab is a humanized monoclonal antibody targeting CD52, a glycosylphosphatidylinositol-anchored surface antigen broadly expressed on lymphocytes and other immune cells. Although currently approved for multiple sclerosis and used in selected transplantation settings, alemtuzumab was among the earliest lymphocyte-depleting biologics explored across a wide spectrum of autoimmune rheumatic diseases. With renewed interest in deep immune-depleting strategies, including CAR-T cells and bispecific T-cell engagers, revisiting the immunobiology and clinical experience of alemtuzumab is timely. This review summarizes current knowledge of CD52 structure, expression, and immunological function, highlighting its dual role as both a co-stimulatory and immunoregulatory molecule. We examine the mechanisms underlying alemtuzumab-induced lymphocyte depletion, subsequent immune reconstitution, and the paradoxical development of secondary autoimmunity. Clinical evidence for alemtuzumab use in rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, idiopathic inflammatory myopathies, ocular inflammatory disease, and Behçet's syndrome, is reviewed, with emphasis on efficacy, durability of response, and safety outcomes. Across multiple refractory disease settings, alemtuzumab has demonstrated the capacity to induce rapid clinical improvement and, in some cases, prolonged drug-free remission. However, treatment is limited by risks of infection, delayed immune reconstitution, and immune dysregulation. We conclude that alemtuzumab remains a potent immunomodulatory option in selected refractory rheumatic diseases, provided that careful patient selection, cautious monitoring, and long-term follow-up are implemented.
    Keywords:  Alemtuzumab; Autoimmune rheumatic diseases; CD52; Immune reset; Immune tolerance; Secondary autoimmunity
    DOI:  https://doi.org/10.1016/j.autrev.2026.104056
  32. Blockchain Healthc Today. 2025 ;8(2):
    Blockchain Applications in Core Healthcare Services: Patient Data, Research, and Institutional Processes.
    Muhammet Damar, Omer Aydin, Fatih Safa Erenay.
       Objective: This research aims to systematically examine the application of blockchain technology in core primary healthcare services, with a particular focus on its ability to enhance data integrity, transparency, and operational efficiency. The objective is to identify and analyze the primary areas where blockchain is being utilized within the health sciences and to evaluate its contributions to secure patient consent, reliable data verification, and the protection of sensitive health information.
    Methods: This study conducted a systematic literature review of research and review articles indexed in the Web of Science Core Collection between January 10 and March 15, 2025. Articles were selected based on predefined search strings targeting blockchain applications in health sciences, as detailed in the search strategy (Figure 1). Bibliometric analysis was performed using VOSviewer and the Biblioshiny interface of R Bibliometrix to identify thematic areas, keyword co-occurrences, and research trends. Overlay and network visualizations were used to reveal temporal patterns and relational structures among keywords. To enhance the scope of the review, supplementary searches were also conducted via Google Scholar, providing additional insight into emerging topics not yet indexed in Web of Science.
    Results: The analysis revealed eight major thematic areas where blockchain is prominently applied: secure patient consent and data management, healthcare supply chain processes, clinical research and monitoring, legal and intellectual property concerns, disease tracking and epidemiological management including COVID-19, insurance and billing systems, organ transplantation logistics, and applications in cancer and pharmaceutical research. The data demonstrate an increasing focus on blockchain's role in enhancing transparency and accountability in both institutional and patient-centered healthcare services.
    Conclusions: Blockchain holds considerable promise for advancing healthcare systems. However, its effective implementation depends on a comprehensive approach that combines technological innovation with supportive policy frameworks and ethical considerations. These findings provide valuable guidance for stakeholders seeking to integrate blockchain in health service delivery.
    Keywords:  blockchain in healthcare; data security; disease management; epidemiology; healthcare services; healthcare supply chain; pharmaceutical research
    DOI:  https://doi.org/10.30953/bhty.v8.408
  33. Data Brief. 2026 Jun;66 112673
    Deploying the common European manufacturing data space: The UNDERPIN and SM4RTENANCE frameworks' perspective.
    Aristotelis Ntafalias, Marcelo J Ambrosio, Alexandros Nizamis, Panagiotis Papadopoulos, Carmen Polcaro, Oscar Lázaro.
      The growing interest in using data in the manufacturing sector has led to an increased need for efficient and secure data sharing among stakeholders. However, technical, business, and regulatory barriers often prevent the full exploitation of manufacturing data. To address these challenges, the European Commission (EC) has introduced the concept of Common European Data Spaces (CEDS) as part of its broader data strategy. These data spaces aim to ensure data sovereignty and interoperability, in compliance with European regulations, facilitating a trusted environment for data exchange. This paper explores the deployment of two key European-funded projects, UNDERPIN and SM4RTENANCE, which are designed to accelerate the development of the CEDS for the manufacturing sector. These initiatives represent the current efforts towards enabling system integration and strengthening data security, while aiming to enhance cross sector collaboration within the industrial ecosystem. The development of UNDERPIN and SM4RTENANCE data spaces play a crucial role in overcoming technical and business barriers, enabling organizations to unlock the full potential of data-driven innovation and improve operational excellence.
    Keywords:  Data sharing; Data space; Digital transformation; Manufacturing industry; Predictive maintenance
    DOI:  https://doi.org/10.1016/j.dib.2026.112673
  34. Immunol Cell Biol. 2026 Apr 05.
    Cytokine armored CAR T cells for cancer immunotherapy.
    Kevin Sek, Kah Min Yap, Woon Xuan Hong, Phillip K Darcy.
      Cytokine armoring of CAR T cells for enhancing the immunotherapy of cancer. Reprogramming of CAR T-cell phenotypes through (a) IL-158 or (b) IL-9Rα9 engineering. Reprogramming of the tumor microenvironment and recruitment of host antitumor immunity through (c) IL-36γ10 or (d) IL-1211,12 engineering. (e) Tumor-inducible cytokine expression utilizing synthetic NFAT or endogenous NR4A2 promoter systems to restrict systemic expression of potent cytokines for improved safety.
    Keywords:  CAR T cells; cytokine armoring; tumor microenvironment
    DOI:  https://doi.org/10.1111/imcb.70112
  35. Mol Biol Rep. 2026 Apr 07. pii: 593. [Epub ahead of print]53(1):
    CAR-T cell therapy in breast cancer management: expanding horizon and overcoming challenges beyond hematologic cancers.
    Kavya P Parekh, Fahad T Alotaibi, Dhvani D Patel, Omar Awad Alsaidan, Bhupendra G Prajapati, Sami I Alzarea, Ala Meshal Aljehani, Mehul R Chorawala.
      
    Keywords:  Breast cancer; CAR-T cell therapy; Chimeric antigen receptors; Human epidermal growth factor receptor 2 (HER2); Immunotherapy; Solid tumor immunology; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s11033-026-11752-8
  36. Clin Rheumatol. 2026 Apr 05.
    Regulatory T cells as a potential treatment for autoimmune inflammatory rheumatic and musculoskeletal diseases.
    Ian C Chikanza, Clementine Sifiso Nomalizo Mnkandla-Khumalo, Lazaros I Sakkas.
      Autoimmune diseases result from the immune system's inability to distinguish between self and non-self, destroying healthy tissue. T regulatory cells (Tregs) are a unique subset of CD4 + T cells, which play a crucial role in immune tolerance and preventing autoimmunity. Their capacity to quell an exaggerated immune reaction establishes them as a potential point for therapeutic intervention. However, utilizing Tregs' intrinsic repressive nature on other immune cells to prevent or halt autoimmunity and inflammation poses challenges in compromising pathogen clearance and in the place of restraining anti-tumor immune responses. This review outlines the biology of Tregs, their position concerning autoimmune rheumatic disease, obstacles to exploiting their therapeutic potential, and the evolution of Treg-based treatment.
    Keywords:  Ankylosing spondylitis (AS); Autoimmune disease; Autoimmune inflammatory rheumatic and musculoskeletal disorders; Diabetes mellitus; Gut immunity; Juvenile idiopathic arthritis (JIA); Psoriatic arthritis; Rheumatoid arthritis (RA); Sarcoidosis; Systemic lupus erythematosus (SLE); Systemic sclerosis; T regulatory cells; Vasculitis
    DOI:  https://doi.org/10.1007/s10067-026-08069-z
  37. Sci Immunol. 2026 Apr 10. 11(118): eaeg7517
    The rise of spatial TCR profiling: Emerging technologies and open challenges.
    Yinglu Tang, Tao Wang.
      High-definition spatial TCR profiling illuminates how clonal identity and T cell state are coordinated in the tumor microenvironment (see related Research Article by McCord et al.).
    DOI:  https://doi.org/10.1126/sciimmunol.aeg7517
  38. Health Aff (Millwood). 2026 Apr;45(4): 356-360
    'Most Favored Nation' Drug Pricing: An Idea To What End?
    Andrew W Mulcahy.
      US prices for brand-name drugs are substantially higher than those in other countries. Recent "most favored nation" proposals aim to simultaneously lower US prices through international reference pricing while increasing prices in other countries toward parity with the US. Although most favored nation policies have some merit, the challenge is for the US to establish the point at which they will have succeeded-that is, when the resulting net prices paid for brand-name drugs are "right" from a US-focused, value-oriented perspective. Without investments in US health technology assessment research, this crucial endpoint will remain difficult to define.
    DOI:  https://doi.org/10.1377/hlthaff.2026.00184
  39. Trials. 2026 Apr 09. pii: 289. [Epub ahead of print]27(1):
    The use of complex clinical trials: a regulatory review.
    Quynh Nguyen, Hue Kästel, Katharina Hees, Benjamin Hofner.
       BACKGROUND: Complex clinical trials offer flexibility in evaluating multiple treatments or diseases simultaneously. These trials often feature adaptive designs, common controls, and the potential to add new arms. However, the increased complexity raises methodological challenges particularly regarding multiple testing or the adequate choice of control groups. Despite guidance from regulatory bodies like the European Medicines Agency and the U.S. Food and Drug Administration, uncertainties remain about the regulatory acceptance of these trials.
    METHODS: This systematic review examines scientific advice procedures of products in the remit of the Paul-Ehrlich-Institut for complex clinical trials to highlight key concerns and regulatory feedback. We identified 30 scientific advice procedures corresponding to 29 different complex clinical trials.
    RESULTS: Our findings reveal an increasing number of complex trial designs proposed by applicants. A lack of multiplicity control due to multiple arms was generally considered acceptable by regulators in exploratory trials and if cohorts can be considered independent. Additionally, the use of common control groups is frequently proposed by applicants. The review underscores the importance of pre-planning for new treatment arms, appropriate multiplicity control, and the definition of control groups in trial designs.
    CONCLUSION: Overall, our findings suggest that regulatory concerns regarding complex trials largely align with those in traditional trial designs, though their complexity requires careful, case-by-case consideration. Early engagement with regulatory agencies can be crucial to ensure the successful design and implementation of these trials.
    Keywords:  Complex clinical trial; Scientific advice; Systematic review
    DOI:  https://doi.org/10.1186/s13063-026-09674-8
  40. Transfusion. 2026 Apr 10.
    Impaired hematopoiesis affects apheresis and CAR T-cell product composition and treatment response.
    Hanna Kuhn, Felix Korell, Angela Hückelhoven-Krauss, Brigitte Neuber, Miriam Stenzinger, Anita Ludwig-Husemann, Maria-Luisa Schubert, Patrick Derigs, Kiavasch Farid, Tim Sauer, Sandra Sauer, Carsten Müller-Tidow, Peter Dreger, Michael Schmitt, Anita Schmitt.
       BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of hematologic malignancies, but its success depends on obtaining sufficient CD3+ T-cell yields during leukapheresis. This can be difficult in heavily pretreated patients, who often show leukopenia and reduced T-cell fitness.
    METHODS: We analyzed 166 leukapheresis products from 154 patients undergoing manufacturing of CD19-directed CAR T-cells, including 146 from non-Hodgkin's lymphoma (NHL) and 20 from acute lymphoblastic leukemia (ALL). Collections were performed for commercial CAR T-cell products (axi-cel, tisa-cel, brexu-cel, liso-cel; n = 121) and the HD-CAR-1 trial with in-house manufacturing (heidagenlecleucel; n = 45).
    RESULTS: In 150/154 patients, a sufficient CD3+ T-cell yield was achieved by a single leukapheresis. Pre-apheresis lymphocyte count strongly predicted CD3+ T-cell yield (p< .001) and was associated with treatment response (p = .044). Impaired hematopoiesis, reflected by reduced nucleated cell count (p< .001), lymphocyte count (p <.001), and hematocrit (p = .017), was linked to poorer collection efficiency. Intensive prior therapies, including stem cell transplantation, reduced CAR T-cell expansion during manufacturing (p = .036). In patients with ALL, higher proportions of effector and CD8+ CAR T-cells in the product correlated with improved clinical outcomes (p = .04; p = .023).
    CONCLUSION: These findings highlight the importance of early leukapheresis, ideally before intensive treatments, to optimize T-cell yield, product quality, and therapeutic efficacy.
    DOI:  https://doi.org/10.1111/trf.70224
  41. Best Pract Res Clin Rheumatol. 2026 Apr 03. pii: S1521-6942(26)00027-6. [Epub ahead of print] 102142
    Malignancy and rheumatic diseases.
    Savannah Bowman, Maria E Suarez-Almazor.
      Several systemic autoimmune rheumatic diseases carry an increased risk of malignancy compared to the general population, including dermatomyositis, Sjogren's disease (SjD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). This is likely a result of chronic inflammation, impaired tumor surveillance related to treatments, and shared risk factors, such as smoking. As treatments for systemic autoimmune rheumatic diseases continue to expand and cancer survival continues to improve, clinicians and patients are increasingly faced with complex decisions regarding the treatment of rheumatic autoimmune diseases in patients with current or prior malignancy. This review describes the risk of malignancy across the most common autoimmune diseases, highlights cancer screening recommendations in this patient population, and examines the evidence on the risk of de novo malignancy, or cancer progression and recurrence with the use of several biologic and targeted synthetic disease-modifying anti-rheumatic drugs. We also highlight important management considerations when selecting therapies to treat autoimmune diseases in patients with current or recent cancer.
    Keywords:  Autoimmune disease; Biologic therapy; Cancer; Targeted therapy
    DOI:  https://doi.org/10.1016/j.berh.2026.102142
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