bims-carter Biomed News
on CAR-T Therapies
Issue of 2026–02–08
forty-two papers selected by
Luca Bolliger, lxBio
  1. Advances in chimeric antigen receptor-natural killer cell therapy: from mechanisms and preclinical studies to clinical application.
  2. Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.
  3. Racial and Socioeconomic Healthcare Disparities in Access to Chimeric Antigen Receptor T (CAR-T) Cell Therapy for Blood Cancers.
  4. Process Systems Engineering in Precision Medicine: Opportunities in Autologous CAR-T Therapy.
  5. Beyond CRISPR: next-gen precision engineering of CAR-NK cells for enhanced persistence, trafficking, and tumor eradication.
  6. From innovation to implementation: Health-system pharmacy integration of cell and gene therapies.
  7. Novel Combination of Irreversible Electroporation and Allogenic Chimeric Antigen Receptor T-Cell Therapy Synergizes Therapeutic Outcomes in a Preclinical Human Pancreatic Cancer Mouse Model.
  8. Optimizing bridging radiotherapy prior to CAR-T cell therapy: an evidence-based approach.
  9. Induced pluripotent stem cell (iPSC)-derived CAR-macrophages: new kids on the block.
  10. How the HTAR will contribute to a value-based decision-making for medicinal products across the EU.
  11. Global Research Landscape in T Cells and Myasthenia Gravis: Trends, Collaborations, and Future Directions.
  12. Synthetic Hybrid Receptors for Safer and Programmable T Cell Therapy.
  13. Beyond Numbers: Uses and Value of In-Trial Interview Data for Regulatory and Health Technology Assessment (HTA) Decision Making.
  14. Cancer immunotherapy insights: key takeaways from the ADSCC bone marrow and cellular therapy congress 2024.
  15. Maximizing Access to Cell and Gene Therapy for Patients with Rare Diseases.
  16. Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.
  17. A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types.
  18. Novel perspectives on extracellular vesicles in autoimmune diseases: immunogenicity, inflammation, and immune surveillance.
  19. From Consensus to Implementation: Advancing Patient-Centered Health Technology Assessment.
  20. The U.S. Food and Drug Administration's Perspective on Chimeric Antigen Receptor T-Cell Therapies for Autoimmune and Rheumatic Conditions.
  21. Methods for information-sharing in network meta-analysis: Implications for inference and policy.
  22. Targeting epigenetic regulators to boost T cell immunotherapy against cancer.
  23. Enhancing CAR- and TCR-mediated targeting of cancer via an immune synapse-stabilizing receptor.
  24. The Food and Drug Administration's role in supporting therapeutic development to address unmet needs: the National Academies report and beyond.
  25. Neurotransmitters: Key regulators of the tumor immune microenvironment.
  26. Regulatory Considerations for Medical Aerosol Products.
  27. Turn CAR T against TAMs.
  28. The dark side of the dot: How melanosomes dim T cell activity.
  29. Digital twins for accelerating drug discovery and development: opportunities and challenges.
  30. A Case Report of HLA 5/10 Cord Blood Cell Engraftment in a Patient with Severe β Thalassemia after Haplo-Cord Stem Cell Transplantation.
  31. The evolution of cellular-based immunotherapy in the treatment of gastric cancer: an overview of clinical trials.
  32. Cell and Gene Therapy in Equine Ocular Disease.
  33. Sialic acids modulate immune responses in cancer: Therapeutic opportunities.
  34. Synergistic immune interactions between T cells and natural killer cells in allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: current status and future directions.
  35. Modulating the Gut Microbiome as a Therapeutic Approach in Multiple Sclerosis: Implications for Gut-Brain Interactions and Immune Pathways: A Narrative Review.
  36. Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.
  37. Enhancing accessibility and impact of digitally enabled clinical trials: the WeShare engagement and equity toolkit.
  38. Barriers and Facilitators of Digital Transformation in Health Care: Mixed Methods Study.
  39. Lung cancer immunotherapy in 2025: where we stand and what comes next?
  40. Shaping immunotherapy through the tumor microenvironment: Translational perspectives.
  41. Digital twins in oncology: From predictive modelling to personalised treatment strategies.
  42. Constructing effectiveness as a general legal principle of public healthcare systems: comparative insights from France, Germany, and England.
  1. Front Oncol. 2025 ;15 1759796
    Advances in chimeric antigen receptor-natural killer cell therapy: from mechanisms and preclinical studies to clinical application.
    Tianyuan Ren, Fengjiang Wang, Xuan Liu, Jun Guo, Sitan Xie.
      Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized cancer treatment, yet its application remains limited by high costs, safety concerns, and challenges in solid tumors. Natural killer (NK) cells offer a promising alternative due to their innate tumor-killing capacity, diverse cell sources, lower risk of graft-versus-host disease and cytokine release syndrome, and potential for "off-the-shelf" production. This review synthesizes recent advances in CAR-NK, focusing on NK-specific CAR engineering strategies, preclinical models across hematological and solid malignancies, and the latest clinical trials up to 2025. We highlight distinctive CAR-NK optimization approaches, such as integration of Fc-binding domains, cytokine armoring, and strategies to overcome tumor microenvironment mediated resistance, that distinguish CAR-NK from CAR-T platforms. Key challenges, including insufficient in vitro expansion, manufacturing scalability barriers, in vivo persistence, and the immunosuppressive effects of the tumor microenvironments (TME), as well as their corresponding potential technical solutions, are critically analyzed. By integrating the latest translational insights, this review aims to provide a forward-looking perspective on CAR-NK as a next-generation immunotherapeutic modality.
    Keywords:  CAR-NK; chimeric antigen receptor (CAR); hematological malignancies; natural killer cells; solid tumor
    DOI:  https://doi.org/10.3389/fonc.2025.1759796
  2. Sci China Life Sci. 2026 Jan 23.
    Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.
    Shi Han, Juan Yue, Haiqiong Zheng, Yue Huang, Delin Kong, Guoqing Wei, Yongxian Hu, He Huang.
      Chimeric antigen receptor-T (CAR-T) cell therapy has made considerable advancements in the treatment of malignant tumors; however, its clinical application continues to face challenges such as low response rates and relapse, which are critical issues requiring urgent resolution. The insufficient functionality of CAR-T cells remains a core factor affecting their clinical efficacy. This article provides a systematic review of various strategies to enhance CAR-T cell functionality, including structural modification and gene editing of chimeric antigen receptor CAR molecules, optimization of manufacturing processes, enhancement of CAR-T cells to counteract the inhibitory tumor immune microenvironment, and combination therapies with other drugs. In terms of optimizing CAR molecules, particularly the development of dual-target CARs, this approach not only effectively prevents antigen escape but also significantly enhances the activation, proliferation, and anti-tumor efficacy of CAR-T cells. Gene editing technology offers new opportunities to improve the persistence, proliferative capacity, and anti-tumor activity of CAR-T cells, thereby enhancing their function and reducing disease relapse. Furthermore, epigenetic regulation augments the adaptability of CAR-T cells, strengthening their anti-tumor effects. Simultaneously, combining CAR-T cell therapy with other immunotherapies provides fresh perspectives for improving overall treatment efficacy. However, challenges remain in areas such as the precision of gene editing, reversibility of epigenetic regulation, and optimization of CAR structures. Future research should focus on refining these strategies and exploring their synergistic applications to maximize the therapeutic potential of CAR-T cell therapy. With ongoing technological advancements, CAR-T cell therapy is poised to achieve groundbreaking applications in a broader range of malignant tumor treatments, offering new hope to patients.
    Keywords:  chimeric antigen receptor T cells; functional enhancement; mechanisms; therapeutic strategies
    DOI:  https://doi.org/10.1007/s11427-025-3061-8
  3. Cancer Med. 2026 Feb;15(2): e71457
    Racial and Socioeconomic Healthcare Disparities in Access to Chimeric Antigen Receptor T (CAR-T) Cell Therapy for Blood Cancers.
    Hasini Warnakulasuriya, Ritika Tiwari.
       BACKGROUND: Health disparities remain a critical global public health challenge, particularly in access to advanced treatments for blood cancers. Racial and socioeconomic factors influence healthcare accessibility, contributing to inequities in patient outcomes. Despite the potential of CAR-T therapy in treating blood cancers, disparities in financial resources, education, gender, and race hinder equitable access. This study evaluates literature on CAR-T therapy to identify access disparities and proposes policy recommendations.
    METHODS: The PRISMA-ScR guidelines were followed for study selection and reporting. A comprehensive search strategy was used across databases like PubMed and Google Scholar, using keywords and MeSH terms. Inclusion criteria included peer-reviewed studies in English since 2000. A basic quality appraisal was conducted to ensure the relevance and credibility of included studies, despite the diversity of study designs and the primary focus on mapping key themes across the literature.
    RESULTS: Twenty-five relevant (25) studies, including analytical studies, observational studies, and literature reviews, were analyzed. Findings indicate significant racial and socioeconomic disparities in CAR-T therapy accessibility, with financial constraints, lack of awareness, and systemic biases limiting equitable distribution. Challenges include high treatment costs, lack of insurance coverage, and underrepresentation of minority groups in trials.
    CONCLUSION: Addressing these disparities requires targeted policy interventions, increased funding, and improved patient education. Continued research and collaboration are essential to ensure equitable access for all individuals.
    Keywords:  CAR‐T cell therapy; blood cancers; health disparities; health equity; minority groups
    DOI:  https://doi.org/10.1002/cam4.71457
  4. Eng Life Sci. 2026 Feb;26(2): e70067
    Process Systems Engineering in Precision Medicine: Opportunities in Autologous CAR-T Therapy.
    B Wayne Bequette.
      Autologous chimeric antigen receptor (CAR)-T therapies have given hope to many cancer patients whose other lines of treatment have failed. Unfortunately, limited manufacturing capability has resulted in many patients dying while on a waitlist. Similarly, since clinical trial treatments are personalized, it is difficult to treat many patients simultaneously, resulting in longer clinical trials. Therapeutic production often takes over 4 weeks, so a product failure means that a patient may need to wait another month for treatment, putting them at severe risk for disease progression. The labor-intensive manufacturing process has led to therapeutic costs of roughly $500,000 per treatment, which can be reduced by better automation and shorter manufacturing times. The goals of this article are to review CAR-T therapeutics development, manufacturing, and treatment, and to encourage the development of data analytics-based multi-scale decision support tools for all humans "in the loop." A systems approach is needed since prior treatments and current state of health (including the immune system and microbiota), initial cell quality, manufacturing failure, bridging and lymphodepletion therapy before infusion, and supply chain management, all impact treatment success. Continuous updates as more patient data are made available can lead to better treatment recommendations and outcomes.
    Keywords:  CAR‐T; automation; biomanufacturing; immunotherapy; personalized medicine
    DOI:  https://doi.org/10.1002/elsc.70067
  5. Cancer Cell Int. 2026 Feb 05.
    Beyond CRISPR: next-gen precision engineering of CAR-NK cells for enhanced persistence, trafficking, and tumor eradication.
    Aiyun Dong, Hamed Soleimani Samarkhazan, Farzaneh Tavakoli.
      Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising "off-the-shelf" alternative to CAR-T cells, offering a superior safety profile and inherent multi-antigen targeting capabilities. However, their clinical potential is constrained by the "CRISPR ceiling", a set of practical limitations of DSB-based CRISPR-Cas9 such as DNA double-strand break (DSB)-associated chromosomal rearrangements and p53-mediated fitness loss, low efficiency for safe, large, multicistronic knock-ins, and rigid promoter-driven transgene expression that can cause tonic signaling. Importantly, next-generation, DSB-free base and prime editors reduce or eliminate the DSB-associated genotoxic stress observed with nuclease cutting, CRISPR-associated transposases now enable programmable, targeted insertion strategies that can accommodate larger cassettes, and synthetic/epigenetic circuits provide dynamic, context-dependent transgene control that avoids constitutive promoter-driven tonic signaling. This review explores technological approaches beyond conventional CRISPR, highlighting next-generation precision engineering tools that may enable improved CAR-NK therapies and represent potential advances in safety and efficacy. We detail how base editing, epigenetic reprogramming, targeted transposon systems, and synthetic biology circuits can be synergistically integrated to overcome critical clinical challenges. These advanced technologies enable the precise enhancement of three fundamental pillars of efficacy: Persistence through endogenous cytokine armoring and metabolic engineering; Trafficking via chemokine receptor matching and stromal barrier degradation; and Tumor Eradication using logic-gated targeting, immunomodulatory payloads, and bispecific engagers. By synthesizing these cutting-edge advances, we provide a roadmap for developing next-generation CAR-NK cells capable of durable, potent, and safe antitumor responses against both hematological and solid malignancies, ultimately forging a new frontier in accessible cellular immunotherapy.
    Keywords:  Allogeneic cell therapy; CAR-NK cells; Precision genome editing; Solid tumor immunotherapy; Synthetic biology
    DOI:  https://doi.org/10.1186/s12935-026-04219-0
  6. Transfusion. 2026 Feb 02.
    From innovation to implementation: Health-system pharmacy integration of cell and gene therapies.
    Danielle Pennock, Kelin Wheaton, Blake Shay, Jill Blind.
       BACKGROUND: Cell and gene therapies (CGTs) represent a paradigm shift in modern medicine, offering targeted and potentially curative options for complex and rare diseases. Their integration into health-system pharmacy practice requires alignment with the medication-use process to ensure safety, efficacy, and compliance.
    OBJECTIVE: To propose a practical framework for integrating CGTs into health-system pharmacy workflows, while addressing clinical, operational, and financial considerations.
    SUMMARY: The framework encompasses four domains: (1) evaluation-strategic assessment of pipeline therapies, including clinical, operational, and financial readiness; (2) clinical integration-formulary review, electronic medical record configuration, clinical pathways, and standard operating procedures development; (3) operational pharmacy integration-establishing infrastructure for receipt, storage, handling, and dispensing, supported by training and process improvement; and (4) financial integration-implementing reimbursement strategies, payment workflows, and budgeting to mitigate financial risk. These recommendations draw on the institutional experience of the authors and emerging standards from professional organizations.
    CONCLUSION: Proactive planning and interdisciplinary collaboration are essential for successful CGT implementation. Health-system pharmacists are uniquely positioned to lead these efforts, ensuring patient safety, operational efficiency, and financial sustainability as advanced therapeutics reshape the healthcare landscape.
    DOI:  https://doi.org/10.1111/trf.70110
  7. Research (Wash D C). 2026 ;9 1105
    Novel Combination of Irreversible Electroporation and Allogenic Chimeric Antigen Receptor T-Cell Therapy Synergizes Therapeutic Outcomes in a Preclinical Human Pancreatic Cancer Mouse Model.
    Edward Jacobs, Julio Arroyo, Sam Salemizadeh Parizi, Wei Guo, Yong Lu, Rafael Davalos.
      Irreversible electroporation (IRE) is a nonthermal ablation modality used clinically for treating unresectable tumors while preserving vital structures through controlled application of pulsed electric fields. Previous data suggest that patient outcomes are enhanced with the induction of an anti-tumor immune response, but current research focuses on using immune checkpoint inhibitors, which function through conventional immune pathways that may be down-regulated by cancer or dysregulated by chemo-induced lymphodepletion. Chimeric antigen receptor (CAR) T cells overcome this limitation, as they are engineered with synthetic receptors that redirect lymphocytes to recognize and target cells expressing tumor-specific structures. CARs are engineered to have an increased binding affinity compared to in situ T-cell binding, amplify internal stimulation cascades, and release pro-inflammatory cytokines that can modulate the endogenous immune system. However, there are still major limitations for adoptive cell therapies in solid tumors, including life-threatening on-target off-tumor cytotoxicity, antigen escape, and failure to infiltrate and persist in solid tumors. Given the substantial evidence that IRE overcomes many of the challenges associated with immune infiltration and persistence in solid tumors, there is a strong premise for using targeted cell therapies following IRE, which would then target residual cancer that could repopulate the lesion. Here, we present the first proof-of-concept combination of IRE with CAR T cells. We validated that the cell membrane CAR target is not affected in electroporated cells that survive IRE, allowing for subsequent binding and elimination of residual tumor. The research demonstrates the feasibility and synergy of a novel combination of 2 clinically used techniques.
    DOI:  https://doi.org/10.34133/research.1105
  8. Crit Rev Oncol Hematol. 2026 Feb 04. pii: S1040-8428(26)00068-5. [Epub ahead of print] 105181
    Optimizing bridging radiotherapy prior to CAR-T cell therapy: an evidence-based approach.
    Pierre Loap, Clémentine Sarkozy, Remi Dendale, Youlia Kirova.
      Bridging radiotherapy has emerged as a valuable strategy to ensure optimal conditions for chimeric antigen receptor T-cell (CAR-T) therapy in relapsed or refractory hematologic malignancies. By controlling disease burden and maintaining clinical stability in the interval between leukapheresis and CAR-T infusion, it helps counteract the risk of tumor progression that can diminish treatment efficacy. Evidence from diffuse large B-cell lymphoma (DLBCL) and other lymphomas supports the use of hypofractionated radiotherapy to achieve rapid local control with minimal delays, while preliminary data in multiple myeloma expand its applicability. Radiotherapy's immunomodulatory effects, including enhanced antigen presentation and inflammation, may bolster CAR-T cell activity, though careful consideration is required to avoid potential immunosuppressive consequences. The optimal integration of bridging radiotherapy encompasses timing after leukapheresis, rapid planning and delivery, judicious choice of fractionation, and close coordination between hematology and radiotherapy teams. Tailoring dose and technique further refines the therapeutic window, minimizing toxicity while maintaining efficacy. These evidence-based practice propositions provide a comprehensive framework for implementing bridging radiotherapy. By outlining indications, workflow, fractionation schemes, and technical approaches, these guidelines facilitate the seamless incorporation of radiotherapy into CAR-T therapy protocols, ultimately aiming to improve patient outcomes through enhanced disease control and synergistic antitumor immunity.
    Keywords:  Bridging; CAR-T; Lymphoma; Radiotherapy
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105181
  9. Exp Hematol. 2026 Feb 01. pii: S0301-472X(26)00017-2. [Epub ahead of print] 105384
    Induced pluripotent stem cell (iPSC)-derived CAR-macrophages: new kids on the block.
    Fucai Zhu, Zhongfa Chen, Yan Yu, Lanlan Rao, Guifang Lin, Jing Deng, Qiuhua Yu.
      Remarkable outcomes of chimeric antigen receptor (CAR)-T cell therapy in treating hematologic malignancies have inspired parallel efforts to harness the potential of other immune cell types for CAR-based immunotherapy. These efforts aim to overcome the existing limitations of CAR-T cell therapy. In recent years, CAR-macrophages (CAR-MACs) have shown astonishing efficacy in cancer treatment, leading to the approval of several CAR-MAC products for clinical trials. The lack of T-cell receptor (TCR) expression allows them to be used in allogeneic settings and as off-the-shelf products. Within the tumor microenvironment (TME), they can suppress tumor growth via multimodal mechanisms, including CAR-dependent and CAR-independent activities. They can also remodel the TME and prime other immune cells to enhance antitumor responses. Despite these merits, obtaining a sufficient number of MACs from traditional sources is challenging or is subject to regulatory hurdles. This review explores induced pluripotent stem cells (iPSCs) as an emerging source for generating iPSC-derived CAR-MACs (CAR-iMACs). In this regard, we begin with an overview of MACs and their conventional sources, and discuss the advantages of iPSCs over these traditional sources. After that, the technical procedures for generating iPSCs and differentiating them into functional CAR-iMACs are comprehensively discussed. Finally, we explore the preclinical and clinical advances in CAR-iMAC therapy.
    Keywords:  CAR-macrophages; Chimeric antigen receptor (CAR); Immunotherapy; Induced pluripotent stem cells (iPSCs)
    DOI:  https://doi.org/10.1016/j.exphem.2026.105384
  10. Br J Clin Pharmacol. 2026 Feb 05.
    How the HTAR will contribute to a value-based decision-making for medicinal products across the EU.
    Roisin Adams, Michal Stanak.
      The European Union Health Technology Regulation 2021/2282 (HTAR) introduces joint assessment of health technologies (including medicinal products and medical devices) across EU Member States. It was signed into law in 2021 and came into full force in January 2025. HTAR includes some core domains such as Joint Clinical Assessment (JCA), which refers to the relative effectiveness assessment of new technologies that have submitted a marketing authorization application to the EMA. It further includes Joint Scientific Consultation, which allows health technology developers to seek advice at an early stage in order to plan evidence generation in line with HTA needs. Such joint work will feed into respective national decision-making processes. While a JCA report will arguably fit directly into appraisal processes based on an added benefit framework, countries performing cost-effectiveness appraisal will be expected to incorporate a JCA into their value frameworks. In assessing the value of a new technology, however, HTA agencies face challenges stemming from the complexity of new technologies, a weakened evidence paradigm and a delay in access. The authors argue that HTAR can contribute towards solving some of the challenges through the reestablishment of evidence standards even for complex technologies, reduction of redundancies and a build-up of assessment capacity. Together with the suggested changes in the pharmaceutical regulation, HTAR may shorten the delay for late-access countries. HTAR is argued to be a major step towards a longer-term goal of equitable, efficient and high-quality healthcare in Europe, potentially leading towards the direction of one European HTA body.
    Keywords:  HTA; HTAR; health technology; medicinal products; value
    DOI:  https://doi.org/10.1002/bcp.70437
  11. Mol Neurobiol. 2026 Feb 05. 63(1): 419
    Global Research Landscape in T Cells and Myasthenia Gravis: Trends, Collaborations, and Future Directions.
    Yingying Jiao, Zien Lin, Shiwen Fan, Aidong Ji, Xiaoqing Cai, Yaoqi Wu, Yafang Song.
      Myasthenia gravis (MG) has emerged as a significant global public health concern. A growing number of studies have focused on T cells in the pathophysiology of MG given that they regulate the immune response and affect autoantibody formation, which leads to the progression of the disease. Currently, there are no comprehensive studies on T cells and MG. Therefore, it is imperative to address this key area through bibliometric analysis and exploration of molecular mechanisms, which will provide essential guidance for investigating fundamental pathological processes and enhancing clinical management. Firstly, we investigated the Web of Science™ Core Collection and the PubMed database for relevant literature, assessing temporal and spatial distribution, the leading research center, key investigators, influential journals, topic hotspot evolution, references, and keywords. CiteSpace and VOSviewer were used for visualizing. Over the past decade, research on T cells and MG has gained curiosity and enthusiasm. Then, we reviewed key research areas which are the roles of T cell subsets, B cell subsets, cytokines, ICI-MG, and new immunotherapy, etc. Notably, we also highlighted emerging T cell-related research fields, such as CAR-T cell therapy and extracellular vesicle-based drug delivery. These cutting-edge directions hold particular promise for promoting interdisciplinary studies and personalized therapies, ultimately bridging the gap between foundational research and clinical implementation.
    Keywords:  Bibliometric analysis; Immunotherapy; Mechanisms; Myasthenia gravis; T cell
    DOI:  https://doi.org/10.1007/s12035-025-05523-y
  12. bioRxiv. 2026 Jan 23. pii: 2026.01.22.701150. [Epub ahead of print]
    Synthetic Hybrid Receptors for Safer and Programmable T Cell Therapy.
    Maxwell G Foisey, Julie Garcia, Xun Li, Xiaoyu Yang, Claire Hilburger, Chloe Thienpont, Alejandro Chaves-Martinez, Serkan Belkaya, Tina Truong, Iowis Zhu, Raymond Liu, Axel Hyrenius-Wittsten, Ricardo Almeida, Brian R Shy, Greg M Allen, Sarah Wyman, Kole T Roybal.
      Engineered T cell therapies have achieved significant clinical success in hematological malignancies but remain largely ineffective in solid tumors. Overcoming this limitation requires strategies that enhance T cell function while avoiding systemic immune toxicities and pathological T cell states. Existing approaches typically rely on constitutive gene overexpression or suppression to augment potency or remodel the tumor microenvironment, but these strategies frequently lead to dysregulated immune activation and dose-limiting toxicity. Here, we present Hybrid Receptors (Hybrid-Rs), a modular receptor platform that integrates features of chimeric antigen receptors (CARs) and SyNthetic Intramembrane Proteolysis Receptors (SNIPRs) to couple antigen-dependent T cell activation with programmable gene regulation. Hybrid-Rs enable precise, context-dependent control of T cell potency, differentiation states, and conditional expression of secreted immunotherapeutic payloads with otherwise prohibitive toxicity. Hybrid-Rs are readily humanized and compatible with precision genome editing in primary human T cells, providing a direct and practical path to clinical translation.
    DOI:  https://doi.org/10.64898/2026.01.22.701150
  13. Patient. 2026 Feb 02.
    Beyond Numbers: Uses and Value of In-Trial Interview Data for Regulatory and Health Technology Assessment (HTA) Decision Making.
    Carla Dias-Barbosa, Miriam Kimel, Paulina Rolska-Wojcik, Karen Bailey, Olabimpe R Eseyin, Mona L Martin.
      This research explores the growing importance of qualitative in-trial research (ITR) in regulatory and health technology assessment (HTA) decision making. Since 2020, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have emphasized incorporating patient experience data into drug development and approval. We reviewed regulatory guidance documents, drug approval records, and HTA reports from January 2017 to March 2025. This included labels and reviews for new drug applications from the FDA and EMA, the Patient-Focused Drug Development guidance series, guidance on rare diseases, oncology, and gene therapy, and methodological guidance from HTA bodies in Scotland, the UK, France, Germany, Italy, and Spain. From more than 1000 drug applications assessed by both regulatory agencies, only ten and eight products (from the FDA and EMA, respectively) included ITR, with 55% of these for rare diseases. Both agencies used ITR data to gain insights into symptoms and patient experiences, the relevance of patient-reported outcome concepts, and meaningful changes in symptoms or treatment benefits; and to support the interpretation of meaningful score or endpoint changes. Two products included ITR data in both FDA and EMA reviews/labels. Three HTA bodies published guidance documents on qualitative research, with only two products out of eight reviewed including qualitative data in HTA reports.Despite increasing use, ITR in regulatory submissions and HTA reviews remains limited. Early planning and alignment of ITR objectives with regulatory and HTA requirements are needed to enhance the relevance and impact of qualitative evidence in drug development and healthcare decision making.
    DOI:  https://doi.org/10.1007/s40271-025-00795-x
  14. Front Immunol. 2025 ;16 1650023
    Cancer immunotherapy insights: key takeaways from the ADSCC bone marrow and cellular therapy congress 2024.
    Gisela Maria Suárez Formigo, Zaima Mazorra, Cinthia Olexen, Tamara Menéndez, Loubna Abdel Hadi, Rupert Handgretinger, Antonio Alfonso Bencomo Hernandez, Inas El Najjar, George Coukos, Helen Sabzevari, Catherine Bollard, Daniel Couriel, David Wald, Mohamad Hamieh, Javier Briones, Fatima Al Kaabi, Yendry Ventura-Carmenate.
      The rising global cancer burden underscores the urgent need for innovative and effective therapies. Molecular and cellular immunology advances have revolutionized cancer immunotherapy, transforming laboratory discoveries into clinical breakthroughs. The Second Bone Marrow Transplant and Cellular Therapy Congress, held in Abu Dhabi, United Arab Emirates (UAE), on October 26th - 27th, 2024, and sponsored by the Abu Dhabi Stem Cells Center (ADSCC), convened global experts to discuss cutting-edge developments in adoptive cell transfer (ACT); chimeric antigen receptor T-cell (CAR-T) therapy, tumor-infiltrating lymphocyte (TIL) engineering and T-cell receptor (TCR) innovations. Discussions covered key challenges such as tumor microenvironment (TME) resistance, antigen escape, manufacturing complexity, cost-effectiveness, and accessibility. Experts emphasized the crucial role of biomarker identification in optimizing patient selection and improving treatment efficacy. Additionally, emerging strategies were highlighted to enhance the durability and specificity of cellular therapies, including next-generation CAR-T designs, combination approaches, and novel gene-editing technologies. With over 2,300 participants from academia, research, and healthcare, the event fostered international collaborations and knowledge exchange. The ADSCC continues to play a pivotal role in integrating advanced cellular therapies into healthcare systems, contributing to the expansion of precision oncology in the UAE and beyond. This review analyzes the latest advances in immunotherapy, highlighting their clinical impact, challenges, and future directions in the evolving landscape of cancer treatment, as debated during the congress.
    Keywords:  CAR-T cells; Tumor microenvironment (TME); Tumor-infiltrating Lymphocytes (TILs); adoptive cell transfer; cancer immunotherapy; precision medicine
    DOI:  https://doi.org/10.3389/fimmu.2025.1650023
  15. Hum Gene Ther. 2026 Feb 04. 10430342261422716
    Maximizing Access to Cell and Gene Therapy for Patients with Rare Diseases.
    Terence R Flotte, Guangping Gao.
      
    DOI:  https://doi.org/10.1177/10430342261422716
  16. Adv Sci (Weinh). 2026 Feb 03. e18547
    Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.
    Xinru Zhang, Gulizeba Aimaiti, Yuanye Guan, Yuzhe Sha, Wei Zhou, Jiefeng Shen, Bo Zhao, Wei-En Yuan.
      Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the paradigm in hematological malignancies. However, its efficacy in treating solid tumors remains limited because the immunosuppressive tumor microenvironment (ITME) seriously blocks T cell activation, infiltration, and proliferation. Cytokines, driving potent assisted function by enhanced T cell expansion, persistence, and direct tumor cell killing, have long been acknowledged as promising candidates combined with CAR-T cells to improve treatment outcomes. Despite their preclinical success, significant toxicity occurs in up to one-third of patients induced by powerful immune-mediated cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In these cases, the risk-benefit unbalance is less advantageous for advanced cancer therapies, appealing for a profound understanding of pathophysiological mechanisms of CRS and ICANS, as well as improved management of regulating cytokine production. In this review, we first provide an overview of activation and cytotoxic mechanisms of CAR-T cells. Second, obstacles to CAR-T cells in the ITME are introduced in detail. Third, the advanced design of CAR-T engineered cytokines, coupled with current research progress, is described. Furthermore, pathophysiology and clinical features of CRS and ICANS are described in detail. Lastly, prevention and/or intervention approaches of the two above-mentioned toxicities are emphasized both for developing novel therapeutics and maximizing the benefit of patients.
    Keywords:  CAR engineering; CAR‐T cell; CRS; cancer therapy; cytokines
    DOI:  https://doi.org/10.1002/advs.202518547
  17. Proc Natl Acad Sci U S A. 2026 Feb 03. 123(5): e2500319123
    A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types.
    Saeed Ahmad, Kun Xing, Marcelo S F Pereira, Stephanie Castle, Harshana Rajakaruna, Indrani Nayak, William C Stewart, Kyle A Beckwith, Mitchell S Cairo, Meisam Naeimi Kararoudi, Dean A Lee, Jayajit Das.
      Natural killer (NK) cells may be engineered with chimeric antigen receptors (CARs) to recognize tumor-associated antigens which bolsters their antitumor activity. More so than CAR-T cells, CAR-NK cell responses result from an integration of signals from a wider range of innate activating cytotoxic receptors, inhibitory receptors, and adhesion receptors in addition to the engineered CAR, making computational modeling of CAR-NK cell cytotoxicity more difficult than CAR-T cells. Uncovering mechanisms and predicting tumor cell responses to CAR-NK cytotoxicity is essential for improving therapeutic efficacy. The complexity of these effector-target interactions and the donor-to-donor variations in NK cell receptor (NKR) repertoire preclude the use of predictive models based on a single receptor, requiring function to be determined experimentally for each donor, CAR, and target combination. Computational modeling generates frameworks that allow the relationships of these factors to biologic outcomes to be explored without resource-consuming experiments. Here, we developed a computational mechanistic multiscale model which considers heterogenous expression of CARs, NKRs, adhesion receptors, and their cognate ligands, signal transduction, and NK cell-target cell population kinetics. The model is trained with quantitative flow cytometry and in-vitro cytotoxicity data and accurately predicts the short-term, long-term, and in-vivo cytotoxicity of CAR-NK cells. Furthermore, using Pareto optimization we explored the effect of CAR proportion and NK cell signaling on the differential cytotoxicity of CD33CAR-NK cells to cancer and healthy cells. This model can be extended to predict CAR-NK cytotoxicity across many antigens and tumor targets and serves as a tool to mechanistically explore CAR-NK signaling and biology.
    Keywords:  CAR-NK; cytotoxicity; multiscale modeling; quantitative flow cytometry; receptors
    DOI:  https://doi.org/10.1073/pnas.2500319123
  18. J Clin Invest. 2026 Feb 02. pii: e194715. [Epub ahead of print]136(3):
    Novel perspectives on extracellular vesicles in autoimmune diseases: immunogenicity, inflammation, and immune surveillance.
    Yin Zhao, Xing Lyu, Xiuhua Wu, Yu Liu, Na Zhang, Wei Wei, Ming-Lin Liu.
      Cells release extracellular vesicles (EVs) with cargo that originates from distinct subcellular compartments, including the nucleus, cytoplasm, and plasma membrane. Given their diverse cargo, EVs play multiple roles in physiology and pathology, including in immune dysregulation and autoimmune pathogenesis. For example, EVs can act as autoantigens by transporting immunogenic molecules from the nucleus or cytoplasm, whereas EVs carrying membrane-bound MHCs from antigen-presenting cells can activate adaptive immunity by presenting self-antigens to T cells. EV-associated cytoplasmic peptidases or proteasomes contribute to immune regulation by modulating antigen processing and presentation. Moreover, EVs also drive inflammatory responses by shuttling a variety of proinflammatory molecules that sustain autoimmune responses. Intriguingly, emerging evidence indicates that EVs might contribute to autoimmune surveillance by activating cytosolic surveillance sensors, modulating immune checkpoints, regulating NK/T cell cytotoxicity, and altering macrophage and DC phagocytosis, representing an exciting and underexplored frontier in autoimmune research. By tackling critical knowledge gaps, this Review explores the emerging roles of EVs and their diverse cargo in driving autoimmune diseases, suggesting new perspectives on their potential as innovative therapeutic targets.
    DOI:  https://doi.org/10.1172/JCI194715
  19. Value Health. 2026 Jan 29. pii: S1098-3015(26)00030-6. [Epub ahead of print]
    From Consensus to Implementation: Advancing Patient-Centered Health Technology Assessment.
    Lharra Mae C Postrano.
      
    DOI:  https://doi.org/10.1016/j.jval.2025.11.022
  20. Ann Intern Med. 2026 Feb 03.
    The U.S. Food and Drug Administration's Perspective on Chimeric Antigen Receptor T-Cell Therapies for Autoimmune and Rheumatic Conditions.
    Anam Tariq, Vijay Kumar, Vinay Prasad.
      
    DOI:  https://doi.org/10.7326/ANNALS-25-04559
  21. Res Synth Methods. 2025 Mar;16(2): 291-307
    Methods for information-sharing in network meta-analysis: Implications for inference and policy.
    Georgios F Nikolaidis, Beth Woods, Stephen Palmer, Sylwia Bujkiewicz, Marta O Soares.
      Limited evidence on relative effectiveness is common in Health Technology Assessment (HTA), often due to sparse evidence on the population of interest or study-design constraints. When evidence directly relating to the policy decision is limited, the evidence base could be extended to incorporate indirectly related evidence. For instance, a sparse evidence base in children could borrow strength from evidence in adults to improve estimation and reduce uncertainty. In HTA, indirect evidence has typically been either disregarded ('splitting'; no information-sharing) or included without considering any differences ('lumping'; full information-sharing). However, sophisticated methods that impose moderate degrees of information-sharing have been proposed. We describe and implement multiple information-sharing methods in a case-study evaluating the effectiveness, cost-effectiveness and value of further research of intravenous immunoglobulin for severe sepsis and septic shock. We also provide metrics to determine the degree of information-sharing. Results indicate that method choice can have significant impact. Across information-sharing models, odds ratio estimates ranged between 0.55 and 0.90 and incremental cost-effectiveness ratios between £16,000-52,000 per quality-adjusted life year gained. The need for a future trial also differed by information-sharing model. Heterogeneity in the indirect evidence should also be carefully considered, as it may significantly impact estimates. We conclude that when indirect evidence is relevant to an assessment of effectiveness, the full range of information-sharing methods should be considered. The final selection should be based on a deliberative process that considers not only the plausibility of the methods' assumptions but also the imposed degree of information-sharing.
    Keywords:  aggregate-level network meta-analysis; borrowing strength; evidence extrapolation; information-sharing; multi-parameter evidence synthesis
    DOI:  https://doi.org/10.1017/rsm.2024.17
  22. Cell Biosci. 2026 Feb 03.
    Targeting epigenetic regulators to boost T cell immunotherapy against cancer.
    Tiaojiang Xiao, Ying E Zhang.
      Epigenetic regulation is crucial in directing T-cell differentiation, function, and fate, thereby influencing the success of T-cell-based immunotherapies. This review begins with an overview of the evolution of T-cell immunotherapies in cancer treatment. We then examine key epigenetic regulators-such as DNA methylation, mRNA methylation, and histone methylation-and their roles in shaping T-cell states during infection and tumorigenesis. The contributions of these regulators to T-cell exhaustion and lineage commitment are discussed in the context of immunotherapy efficacy. We highlight recent advances in targeting epigenetic pathways to enhance CAR-T and TCR-based therapies and conclude with current challenges and emerging strategies to improve the durability and effectiveness of adoptive T-cell therapies.
    Keywords:  Chromatin modification; Epigenetic regulator; T-cell based immunotherapy; Tumor microenvironment (TME)
    DOI:  https://doi.org/10.1186/s13578-026-01533-y
  23. Nat Commun. 2026 Feb 04. 17(1): 1349
    Enhancing CAR- and TCR-mediated targeting of cancer via an immune synapse-stabilizing receptor.
    Chiou-Tsun Tsai, Jorge Ibanez-Vega, Pan Yin, Robert Teis, Norihiro Watanabe, Tadahiro Honda, Mikhail Valkov, Peter J Chockley, Lourdes Asenath Jimenez Madrigal, Giedre Krenciute, Maksim Mamonkin.
      Heterogeneity in antigen expression on cancer cells limits clinical benefit of engineered T-cell therapies and underpins treatment resistance through antigen escape. Here, we present a strategy to improve recognition and lysis of tumors with suboptimal antigen expression through a separate engineered receptor that selectively boosts cytotoxic signaling and immune synapse formation. This synapse-stabilizing receptor (SSR) harbors a modified linker for activation of T cells (LAT) endodomain that amplifies CD3ζ signaling upon binding to a secondary tumor antigen resulting in an augmented Ca2+ flux, activation of MAPK and NF-kB signaling, maturation of immune synapse, and enhanced T-cell degranulation. Removing C-terminal amino acids 178-233 in the LAT endodomain (LAT177) was necessary to minimize SSR-mediated cytotoxicity. In models of acute myeloid leukemia, we show that a CD38-targeting SSR boosts cytolysis of antigen-low cancer cells via a C-type lectin-like molecule-1 (CLL1)-specific chimeric antigen receptor (CAR) and a survivin-specific T cell receptor (TCR). Unlike another CAR, SSR does not produce significant cytotoxicity against normal CD38+ tissues. Our study thus shows that SSR arming enhances targeting of antigenically heterogeneous cancers without compromising safety and selectivity of therapeutic T cells.
    DOI:  https://doi.org/10.1038/s41467-025-65897-4
  24. Health Aff Sch. 2026 Jan;4(1): qxag013
    The Food and Drug Administration's role in supporting therapeutic development to address unmet needs: the National Academies report and beyond.
    Sanket S Dhruva, Stacie B Dusetzina, Kathryn A Phillips, Holly Fernandez Lynch.
      Despite substantial progress, many serious diseases continue to lack safe and effective therapies. Building on a recent National Academies consensus study report that offers several recommendations to better align investments in therapeutic development with unmet needs, in this commentary, we focus on the Food and Drug Administration's role in advancing this goal. Historically, FDA has encouraged investment where market incentives fall short, undertaken efforts to address broad scientific challenges, and administered programs to expedite development and review of drugs targeting unmet needs. Under the second Trump administration, FDA has launched several initiatives that continue these key themes, although some have been controversial, primarily due to concerns about resource sufficiency and the potential for political interference. Regarding other domains addressed by the National Academies report, FDA has recently given mixed signals on its commitment to upholding rigorous approval standards; paid limited attention to noted gaps, including improving rigorous postmarket evidence generation and validating the surrogate markers often used to support product approval; and failed to ensure adequate financial and human resources to support the agency's critical work. Engagement with the National Academies report's recommendations can help ensure that FDA continues to advance progress toward addressing unmet medical needs.
    Keywords:  FDA; expedited pathways; innovation; regulation
    DOI:  https://doi.org/10.1093/haschl/qxag013
  25. Semin Immunol. 2026 Jan 29. pii: S1044-5323(26)00002-3. [Epub ahead of print]81 102015
    Neurotransmitters: Key regulators of the tumor immune microenvironment.
    Liubo Zhang, Wei Jing, Yunbo Li, Yu Ping, Yi Zhang.
      Recent studies have revealed that neurotransmitters, as a class of important signaling molecules, have functional roles that extend beyond the traditional nervous system and play critical regulatory functions in the tumor immune microenvironment. Research has demonstrated that various classical neurotransmitters and their receptors are widely expressed in tumor tissues. Through complex receptor-mediated signaling networks, neurotransmitters dynamically regulate the functions of diverse cell types, including tumor cells and immune cells, thereby influencing tumor progression. Based on these discoveries, significant progress has been made in developing innovative drugs targeting neurotransmitter-receptor axes. Multiple agents, such as N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid-A (GABA-A) agonists, and dopamine receptor antagonists, have demonstrated promising antitumor effects in both preclinical studies and clinical trials. This review systematically summarizes the multidimensional regulatory mechanisms of neurotransmitters in tumor immunity and comprehensively discusses recent advances in neurotransmitter-targeted therapies. These findings not only provide a theoretical foundation for developing novel immunotherapeutic strategies based on neurotransmitter modulation but also open new research perspectives for understanding the emerging field of "neuro-immune-tumor" crosstalk.
    Keywords:  Neurotransmitter; Tumor immune microenvironment; Tumor immunology
    DOI:  https://doi.org/10.1016/j.smim.2026.102015
  26. J Aerosol Med Pulm Drug Deliv. 2026 Feb 04. 19412711261420095
    Regulatory Considerations for Medical Aerosol Products.
    Svetlana Lyapustina.
      This article provides a high-level overview of regulatory considerations for medicinal aerosol products around the world. It builds on our previous review and reflects developments related to more recent trends and innovations in science, business, technology, and regulation. All medicines, including medicinal aerosol products, must be approved by an appropriate government agency prior to marketing authorization. Knowing and complying with the requirements of an appropriate regulatory agency (or agencies) is a prerequisite to successful commercialization of any aerosol therapy. The range of governmental regulatory oversight is broad, including inspections of manufacturing sites, evaluations of preliminary data and study protocols before the start of trials in human subjects, evaluations of the sponsor's clinical and in vitro data for the proposed product, approval of final labeling and of postapproval changes to any aspect of the product or manufacturing process, monitoring of adverse event reports, and other areas. The specific regulatory requirements vary by the product type and by country, and they also change over time as the science and technology involved in the development, manufacture, and characterization of pharmaceutical and biological products evolve. In general, in order to obtain marketing authorization, the sponsor must demonstrate to regulators, using data from appropriately designed studies and other relevant documentation, (1) that the product is safe and efficacious for the proposed therapeutic indication in the target patient population, (2) that the product's manufacturing facility follows current good manufacturing practice2-4 and/or quality management systems,5,6 and (3) that appropriate quality control and quality assurance programs are in place, including programs to verify that the product released to the market, as well as product kept in stability-testing environmental chambers, complies with preset quality specifications. For aerosol delivery devices and drug-device or biological-device combination products, the sponsor must also assess the influence of human factors, device robustness, and materials' (bio)compatibility. The sponsor's responsibility to regulators continues after a product's approval in the form of, for example, required compliance with ongoing quality testing, pharmacovigilance monitoring, any postapproval commitments, and qualification of any postapproval changes. This article provides an overview of the regulatory considerations for inhaled and nasal products.
    Keywords:  chemistry manufacturing and controls; clinical trials; good manufacturing practices; regulatory requirements
    DOI:  https://doi.org/10.1177/19412711261420095
  27. Cancer Cell. 2026 Feb 05. pii: S1535-6108(26)00047-4. [Epub ahead of print]
    Turn CAR T against TAMs.
    Alberto Mantovani, Cecilia Garlanda.
      The diversity of tumor-associated macrophages presents a major challenge to the clinical translation of myeloid cell-targeting strategies. In this issue of Cancer Cell, Yagel et al. and Mateus-Tique et al. demonstrate that IL-12 armored CAR T cells effectively target tumor-promoting macrophage populations and reset the microenvironment toward an anti-cancer mode.
    DOI:  https://doi.org/10.1016/j.ccell.2026.01.008
  28. Sci Immunol. 2026 Feb 06. 11(116): eaef9200
    The dark side of the dot: How melanosomes dim T cell activity.
    Ruimin Wang, Etienne Caron.
      Melanoma cells evade immune detection by secreting MHC-peptide-loaded melanosomes that interact with and impair CD8+ TCRs.
    DOI:  https://doi.org/10.1126/sciimmunol.aef9200
  29. Drug Discov Today. 2026 Feb 02. pii: S1359-6446(26)00022-X. [Epub ahead of print] 104617
    Digital twins for accelerating drug discovery and development: opportunities and challenges.
    Sai Phanindra Venkatapurapu, Lindsay Clegg, Andrzej Nowojewski, Holly Kimko, Damilola Olabode, Aarti Sawant-Basak, Karthick Vishwanathan.
      Digital twins can revolutionize drug development and personalized care by accelerating timelines, reducing costs and failure rates, and potentially improving the safety and efficacy of new therapies. In this review, we explore different applications of digital twins across the pharmaceutical value chain, from target discovery and preclinical research to clinical trials, regulatory review, manufacturing and post-market clinical practice. Key challenges, however, remain in data integration, model reliability, regulatory acceptance and data privacy. Overcoming these barriers will require innovation, transparency and collaborative efforts across the healthcare ecosystem to fully realize digital twin potential for patients, healthcare providers and the pharmaceutical industry.
    Keywords:  Digital twins; drug development; drug discovery; machine learning; mathematical models; precision medicine
    DOI:  https://doi.org/10.1016/j.drudis.2026.104617
  30. Ann Clin Lab Sci. 2025 Nov;55(6): 981-987
    A Case Report of HLA 5/10 Cord Blood Cell Engraftment in a Patient with Severe β Thalassemia after Haplo-Cord Stem Cell Transplantation.
    Changling Zhu, Yue Hu, Li Xu, Na Ma.
      β-Thalassemia major (β-TM) is an autosomal recessive genetic disorder characterized by a deficiency in the synthesis of β-globin chains, leading to reduced functional hemoglobin and life-threatening chronic anemia. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for β-TM, with outcomes dependent on stable donor engraftment, donor-derived erythropoiesis, and low transplant-related complications. Herein, we report a case of a 27-month-old male patient with β-TM who achieved successful, sustained engraftment using unrelated umbilical cord blood (UCB) following haplo-cord stem cell transplantation. The patient received a combination of 7/12 HLA-matched haploidentical peripheral blood stem cells (haplo-PBSCs) and 5/10 HLA-matched unrelated UCB. Post-transplant monitoring confirmed exclusive engraftment of UCB (full chimerism via short tandem repeat polymerase chain reaction [STR-PCR]) with complete hematopoietic reconstitution. As of the last follow-up, the patient has maintained disease-free survival for over 36 months without significant chronic graft-versus-host disease (GVHD) and with stable hemoglobin levels (90-130 g/L). This case provides evidence that HLA 5/10 mismatched unrelated UCB can achieve effective engraftment in β-TM patients undergoing haplo-cord transplantation, supporting its potential as an alternative donor source for patients lacking fully matched donors.
    Keywords:  GVHD; HLA mismatch; haploidentical allogeneic hematopoietic stem cell transplantation; unrelated umbilical cord blood; β-thalassemia major
  31. Clin Transl Oncol. 2026 Feb 03.
    The evolution of cellular-based immunotherapy in the treatment of gastric cancer: an overview of clinical trials.
    Lang Wu, Jasur Rizaev, Khaled Fahmi Fawy, Mustafa Jawad Kadham, Nabieva Dildora, Shakhlokhon Kurbanova, Zamira Atamuratova, Asilbek Dauletbaev, Natrayan Lakshmaiya, Raed Fanoukh Aboqader Al-Aouadi.
      Despite advances in patients' healthcare, gastric cancer remains a major health concern around the world with a high annual incidence rate and mortality. This highlights the urgent need to develop more effective therapeutic strategies, particularly for patients in advanced stages of the disease. In the recent decade, cellular-based immunotherapy has achieved remarkable successes in various hematologic malignancies and solid tumors. Nonetheless, until now, no cellular-based immunotherapy has been approved for GC patients. This review aims to provide a holistic view of the current state of cellular-based immunotherapy for GC, its existing bottlenecks, and future directions to harness the potential of cellular-based immunotherapy for GC treatment. In this regard, we explore clinical trials of various types of cellular-based immunotherapy, including chimeric antigen receptor (CAR)-engineered cell therapy, T cell receptor (TCR)-engineered T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, cytokine-induced killer (CIK) cell therapy, and dendritic cell (DC) vaccines. For each type of cellular-based immunotherapy, we discuss existing roadblocks to successful treatment and explore potential solutions that may improve efficacy, including novel targets, combination approaches, and biomarker-driven patient selection.
    Keywords:  Cellular-based immunotherapy; Clinical trials; Gastric cancer; Immunotherapy; Stomach cancer
    DOI:  https://doi.org/10.1007/s12094-025-04175-7
  32. Vet Ophthalmol. 2026 Mar;29(2): e70151
    Cell and Gene Therapy in Equine Ocular Disease.
    Kimberly A S Young, Lauren V Schnabel, Brian C Gilger.
      Equine ocular disease is common and often challenging to treat using traditional methods. This has led to the development of new therapies. Like human medicine, veterinary medicine is adopting cellular and gene therapy as innovative approaches. Equine ocular disease is a particularly promising area for these techniques. Notably, immune-mediated diseases (such as immune-mediated keratitis and equine recurrent uveitis), ulcerative keratitis, and infectious ocular diseases are of interest. Several ocular gene therapy products are approved for use in humans, and more are currently being researched in veterinary medicine. In veterinary practice, cell therapy mainly involves multipotent stromal cells or mesenchymal stem cells (MSCs), which are also widely studied in human medicine. This review aims to summarize the status of cell and gene therapy in equine ocular disease and provide background on the principles behind these treatments, as well as insights from human medicine. Although many in vitro studies and case series exist, a significant research gap remains. Despite growing clinical use, there are limited controlled in vivo studies assessing their safety, routes of administration, or effectiveness.
    DOI:  https://doi.org/10.1111/vop.70151
  33. J Biol Chem. 2026 Feb 04. pii: S0021-9258(26)00115-8. [Epub ahead of print] 111245
    Sialic acids modulate immune responses in cancer: Therapeutic opportunities.
    Eleanor E Bashian, James C Paulson, Peng Wu.
      The development of therapies that boost anti-tumor immunity has transformed cancer treatment. While the efficacy of traditional therapies, such as chemotherapy and radiation therapy, is limited by toxicity and resistance, forms of immunotherapy, including immune checkpoint blockade therapies and engineered cellular therapies, have shown unprecedented success for certain patient populations. Despite these advances, therapeutic resistance remains a significant barrier, and alternative therapies are needed to overcome immune evasion mechanisms. One prominent evasive mechanism utilized by tumor cells is hypersialylation, the overexpression of glycans capped with sialic acid on the cell surface. This review focuses on the immunosuppressive role of sialic acid in cancer and highlights opportunities to target sialic acid and its binding proteins, offering a promising therapeutic perspective to counteract resistance and improve patient outcomes.
    DOI:  https://doi.org/10.1016/j.jbc.2026.111245
  34. Ann Med. 2026 Dec;58(1): 2601404
    Synergistic immune interactions between T cells and natural killer cells in allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: current status and future directions.
    Nan Wang, Hanxue Zheng, Zhengdong Hao, Pingling Yin, Liansheng Zhang, Lijuan Li.
       BACKGROUND: Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy. Current therapeutic strategies include chemotherapy, targeted therapy and haematopoietic cell transplantation (allo-HSCT) and autologous haematopoietic cell transplantation (auto-HSCT). The graft-versus-leukaemia (GVL) effect and graft-versus-host disease (GVHD) in allo-HSCT remain major research foci, with emerging evidence highlighting the synergistic roles of T cells and natural killer (NK) cells in allo-HSCT immunity. This review systematically integrates the cooperative immunological interactions between T cells and NK cells and elucidates their critical significance in post-transplant immunotherapy.
    METHODS: This review systematically summarizes the cytotoxic mechanisms, immune reconstitution processes and related immunotherapeutic approaches involving T cells and NK cells in AML in the context of allo-HSCT and further elucidates their unique role in post-transplant immune regulation from the perspective of coordinated T-cell and NK-cell interactions.
    RESULTS: T cells and NK cells exert synergistic effects in post-transplant immune reconstitution, GVL responses, GVHD regulation and subsequent immunotherapeutic interventions. Early NK-cell reconstitution provides a critical window for the restoration of T-cell function, whereas cytokines derived from T cells, such as IL-2 and IL-15, further enhance NK-cell activity. This dynamic immunological interplay not only shapes the balance between GVL and GVHD, but also informs the development of post-transplant immunotherapeutic strategies.
    CONCLUSION: The dynamic interplay between T cells and NK cells plays a pivotal role in allo-HSCT for AML. This review systematically integrates the cooperative functions of T cells and NK cells within the allo-HSCT immune landscape, offering new perspectives for advancing post-transplant immunotherapy. A deeper understanding of these mechanisms is expected to provide a theoretical foundation for optimizing post-transplant immune interventions in AML patients and for developing more precise therapeutic strategies.
    Keywords:  Acute myeloid leukaemia; NK cells; T cells; allogeneic haematopoietic cell transplantation; graft-versus-host disease; graft-versus-leukaemia effect
    DOI:  https://doi.org/10.1080/07853890.2025.2601404
  35. Brain Behav. 2026 Feb;16(2): e71254
    Modulating the Gut Microbiome as a Therapeutic Approach in Multiple Sclerosis: Implications for Gut-Brain Interactions and Immune Pathways: A Narrative Review.
    Husna Irfan Thalib, Nuha Fatima, Faaleha Heba Fakruddin, Hosna Hamidullah Ali, Sariya Khan, Mohammed Talha Mohammed Zubair, Mable Pereira, Fatma E Sayed Hassan.
       PURPOSE: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by progressive disability. Emerging evidence has implicated gut microbiome dysbiosis, characterized by decreased short-chain fatty acids (SCFAs)-producing taxa and increased pro-inflammatory species, in disturbed immune signaling, T-helper17/T-regulatory cells imbalance, disturbed tryptophan metabolism, and disrupted integrity of the blood-brain barrier. In this review, we summarize the mechanistic and therapeutic insights from studies that have explored the gut microbiome in MS.
    METHOD: We performed a literature search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov from database inception to January 2025; only English-language articles were included, comprising human MS cohorts and preclinical experimental autoimmune encephalomyelitis models. Of these, approximately 95 human and preclinical studies fulfilled the inclusion criteria. Evidence synthesis was narrative, without meta-analysis.
    FINDING: There has been a consistent depletion of beneficial genera such as Faecalibacterium and Roseburia, expansion of Akkermansia muciniphila, and reduction in microbial metabolites such as butyrate, propionate, and neuroactive indole derivatives in MS patients across studies. These changes promote intestinal permeability, exaggerated pro-inflammatory cytokine responses, and microglial activation. The therapeutic approach of restoring microbial balance includes therapies such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Early trials have shown modest improvements in relapse rates, fatigue, immune profiles, and microbiome composition. Results across randomized studies are heterogeneous, with no significant clinical benefit in several. Pilot trials report modest reductions in relapse rate (RR ≈ 0.85) and fatigue (Cohen's d ≈ 0.3), but several double‑blind RCTs showed no significant benefit (p  >  0.05) in up to 40% of participants, highlighting variable effect sizes.
    CONCLUSION: Interventions aimed at the microbiome are promising as adjunct approaches to the treatment of MS, acting principally through the restoration of SCFAs, immune modulation, and strengthening of the gut-brain axis. Larger, longer-term randomized trials are required to confirm clinical efficacy, define responder phenotypes, and inform personalized microbiome-based therapies.
    Keywords:  fecal microbiota transplantation; gut microbiome; multiple sclerosis; neuroinflammation; probiotics
    DOI:  https://doi.org/10.1002/brb3.71254
  36. Adv Sci (Weinh). 2026 Jan 31. e22532
    Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.
    Márk Kerestély, István Narozsny, Levente Szarka, Daniel V Veres, Peter Csermely, Dávid Keresztes.
      Cellular plasticity is crucially important in cancer-induced cell reprogramming, as well as in regeneration therapies in diabetes, Alzheimer's, and Parkinson's diseases. Protein-protein interaction, signaling, and gene regulatory networks are increasingly used to describe plasticity-induced cellular adaptation in disease progression. This review delineates how network analysis of cell plasticity leads to novel therapy options against 1) cancer progression; 2) epithelial-mesenchymal transition-induced metastases; 3) cancer stem cells, and 4) pre-existent drug-resistant cells. Network plasticity-designed sequential and differentiation therapies are also outlined. 55 plasticity-related cancer drug targets are listed, where 20 have already approved drugs, 9 have investigational drugs, and 26 are drug target candidates. The recent expansion of plastic network-driven pancreatic beta cell and neuron regeneration therapies is described in diabetes, as well as in Alzheimer's and Parkinson's diseases, respectively. Finally, six major network-related research gaps and promising future research areas are outlined, including the discovery of plasticity-related cancer signaling pathways and cross-talks, cancer resensitization therapies, and the use of recently available proteome-wide network data and models to find novel cancer cell differentiation cocktails, drug targets, proper timing, and biomarkers of sequential therapies, as well as to perform in silico drug combination screens and in silico clinical trials.
    Keywords:  cellular learning; chromatin plasticity; endoplasmic reticulum stress; epigenetic memory; ferroptosis, intrinsically disordered proteins; molecular chaperones
    DOI:  https://doi.org/10.1002/advs.202522532
  37. ESMO Real World Data Digit Oncol. 2025 Sep;9 100175
    Enhancing accessibility and impact of digitally enabled clinical trials: the WeShare engagement and equity toolkit.
    M A Franzoi, S Everhard, E Gillanders, I Vaz-Luis.
      Digital technologies are advancing rapidly, reshaping the way we design, operate, and execute clinical trials. Digitally enabled trials are particularly well-positioned to accelerate the implementation of oncology research by streamlining key clinical trial processes such as screening, recruitment, consent, data collection, follow-up, and intervention delivery. Ensuring engagement and addressing equity concerns are critical to the success of these trials, especially if the goal is for digital health to act as an equalizer, reducing existing and persistent disparities in oncology care. This perspective emphasizes the development and implementation of a comprehensive toolkit to tackle engagement and equity challenges within digitally enabled clinical trials.
    Keywords:  digitally enabled clinical trials; diversity and inclusion; engagement; health equity; implementation science
    DOI:  https://doi.org/10.1016/j.esmorw.2025.100175
  38. J Particip Med. 2026 Feb 04. 18 e83551
    Barriers and Facilitators of Digital Transformation in Health Care: Mixed Methods Study.
    Marina Veldanova, Polina Glazkova, Elizaveta Krasilnikova, Marina Kazanfarova, Marina Bezuglova, Ekaterina Sosunova, Marina Zhuravleva.
       BACKGROUND: Digital transformation is now a fundamental component of health care systems worldwide. To develop effective digital health strategies, it is essential to examine physicians' perspectives on the barriers and facilitators of implementation, with particular attention to regional and cultural factors influencing technology adoption.
    OBJECTIVE: This study aims to identify and analyze key barriers and facilitators to the implementation of digital health technologies from physicians' perspectives in Russia.
    METHODS: A 2-phase nationwide mixed methods study was conducted involving 460 physicians from various specialties. The first phase comprised in-depth interviews with 10 physicians to develop a specialized questionnaire. The second phase involved a nationwide cross-sectional survey with 450 physicians using the developed questionnaire. Inclusion criteria were working in a Russian city with a population of more than 100,000, age 22 years and older, at least 3 years of specialty experience, and employment in public or private health care institutions. The analysis focused on 4 categories of digital health technologies: remote consultations, remote monitoring, digital diagnostic solutions, and clinical decision support systems.
    RESULTS: The main barriers identified were fear of making erroneous decisions (25% of physicians), technical difficulties (up to 25%), and legal insecurity (21% of physicians). Notably, the barrier profile varied depending on the type of technology. Key drivers for implementation included time saving (59% of physicians), practical benefits (55% of physicians), and legal security (54% of physicians). Additionally, a convenient training organization was a crucial motivator, with the availability of free training (53% of physicians) and provision of study leave (52% of physicians). These facilitators were consistent across all categories of digital solutions. Based on these findings, key recommendations for the implementation of digital transformation in medical organizations were formulated.
    CONCLUSIONS: The findings highlight the need for comprehensive, technology-specific digital implementation strategies to improve health care digital transformation effectiveness, considering physician concerns about decision-making accuracy, technical challenges, and legal frameworks.
    Keywords:  clinical decision support systems; digital health; digital transformation; eHealth; health care innovation; mHealth; physician barriers; remote patient monitoring; technology acceptance; telemedicine
    DOI:  https://doi.org/10.2196/83551
  39. Front Immunol. 2025 ;16 1728163
    Lung cancer immunotherapy in 2025: where we stand and what comes next?
    Jie Han, Zhibo Yang, Hai Zhao.
      Lung cancer continues to be the leading cause of cancer-related mortality worldwide, accounting for more deaths than breast, colorectal, and prostate cancers combined. Over the past decade, the introduction of immunotherapy has reshaped treatment paradigms, offering hope for long-term survival in a disease historically associated with dismal outcomes. The incorporation of immune checkpoint inhibitors (ICIs) into the treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) has improved outcomes across early-stage, locally advanced, and metastatic settings. However, only a fraction of patients derive durable benefit, and challenges remain in overcoming resistance, predicting response, managing toxicity, and ensuring equitable access. This review provides a comprehensive overview of current progress in lung cancer immunotherapy. It discusses the immunobiology of lung tumors, the role of checkpoint blockade across disease stages, mechanisms of resistance, biomarker development, and combination strategies. Emerging modalities, including bispecific antibodies, CAR- and TCR-based cellular therapies, natural killer (NK) cell platforms, cytokine agonists, oncolytic viruses, and vaccines, are explored in depth. We also evaluate the translational significance of preclinical models, toxicity management, and issues of equity and accessibility. Finally, we outline key future directions that may redefine lung cancer immunotherapy in the coming years. Collectively, these advances highlight a transition from broad applications of checkpoint inhibition toward stage-specific, biomarker-driven, and multimodal immunotherapy approaches designed to convert temporary responses into durable remissions and, ultimately, cures.
    Keywords:  CAR-T; biomarkers; combination therapy; immune checkpoint inhibitors; immunotherapy; lung cancer; novel modalities; resistance mechanisms
    DOI:  https://doi.org/10.3389/fimmu.2025.1728163
  40. Crit Rev Oncol Hematol. 2026 Jan 31. pii: S1040-8428(26)00056-9. [Epub ahead of print]220 105169
    Shaping immunotherapy through the tumor microenvironment: Translational perspectives.
    Vansh Vohra, Meenakshi Dhanawat, Rishabh Chalotra, Bharat Bhushan, Garima, Jashan Girdhar, Inamul Hasan Madar, Randhir Singh, Mohammad Fareed.
      The tumour microenvironment (TME) is a simply orchestrator of cancer progression and a principal mediator of resistance to immunotherapy. This review explains the complex immunosuppressive ecosystem of the TME, highlighting mechanisms of immune evasion including the recruitment of regulatory T cells, myeloid-derived suppressor cells, and tumour-associated macrophages; metabolic competition via the Warburg effect and indoleamine 2,3-dioxygenase activity and hypoxia-driven upregulation of immune checkpoints such as PD-L1. We synthesize translational strategies designed to reprogram this hostile niche, moving beyond immune checkpoint inhibitor monotherapy. These approaches encompass metabolic targeting (e.g., MCT1/4, IDO inhibitors), stromal disruption (e.g., CAF inhibition, vascular normalization), and advanced cellular engineering, such as CAR-T cells resistant to exhaustion and cytokine-secreting constructs. We underline the synergy of combination therapies, integrating checkpoint blockade with chemotherapy, radiotherapy, oncolytic viruses, and adenosine pathway antagonists to augment immunogenic cell death and cytotoxic T lymphocyte infiltration. The predictive value of biomarkers including tumour mutational burden, microsatellite instability, and the spatial architecture of tumour-infiltrating lymphocytes is critically appraised. Furthermore, the review explores emerging frontiers such as neoantigen-based vaccines, microbiome modulation, and bispecific antibodies, underscoring their capacity to convert immunologically "cold" tumours into "hot", responsive lesions. By bridging preclinical insights with clinical trial evidence, this review speculates that the precise modulation of the TME is indispensable for unlocking durable, broad-spectrum antitumor immunity and defining the next generation of cancer immunotherapies.
    Keywords:  CAR-T; Cancer immunotherapy; Combination therapies; Immune checkpoint inhibitors; Treg; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105169
  41. Crit Rev Oncol Hematol. 2026 Jan 30. pii: S1040-8428(26)00058-2. [Epub ahead of print]220 105171
    Digital twins in oncology: From predictive modelling to personalised treatment strategies.
    David B Olawade, Emmanuel O Oisakede, Oluwakemi Jumoke Bello, Claret Chinenyenwa Analikwu, Eghosasere Egbon, Adeyinka Ojo.
      The digital twin (DT) concept, originating from engineering disciplines, has emerged as a transformative technology in healthcare, particularly in oncology. A digital twin creates a dynamic, virtual replica of a patient's physiological and pathological state, integrating multi-dimensional data to enable personalised cancer care. Despite growing interest, comprehensive reviews examining the breadth of DT applications in oncology remain limited. This narrative review aims to synthesise current evidence on digital twin applications in oncology, evaluate their potential to transform cancer care delivery, and identify challenges hindering clinical translation. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and IEEE Xplore databases from inception to September 2025. Studies describing DT development, validation, or application in any cancer type were included. Grey literature, conference proceedings, and expert commentaries were also reviewed to capture emerging trends. Digital twins demonstrate applications across the cancer care continuum, including precision treatment selection, radiotherapy optimisation, drug development, immuno-oncology modelling, surgical planning, and survivorship care. Integration of multi-omics data, imaging biomarkers, and artificial intelligence enables dynamic simulation of tumour behaviour and treatment response. However, challenges persist in data integration, model validation, computational scalability, and ethical governance. Digital twin technology holds substantial promise for advancing precision oncology through predictive, personalised, and adaptive care strategies. Addressing current limitations through interdisciplinary collaboration and regulatory framework development is essential for clinical implementation.
    Keywords:  Artificial intelligence; Digital twin; Oncology; Precision medicine; Predictive modelling
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105171
  42. Health Econ Policy Law. 2026 Feb 04. 1-19
    Constructing effectiveness as a general legal principle of public healthcare systems: comparative insights from France, Germany, and England.
    Irene Domenici, Christian Günther, Ulrich Becker.
      In public healthcare systems, effectiveness is a central requirement for determining which services should be offered and reimbursed. Yet, due to its technical nature and to the need for specification through specialised bodies, the nature of this principle remains underexplored. This article bridges the gap by conducting a comparative analysis of effectiveness' operation in three distinct healthcare systems: Germany, France, and England. We argue that effectiveness can be recognised as a foundational legal principle governing reimbursement decisions, revealing a substantive and a formal dimension. Substantively, effectiveness requires a consideration of an intervention's ability to bring about a clinical benefit, accounting both for its desired outcomes and its risks. The applied evidentiary standard calls for a careful scrutiny of the available scientific evidence, as well as the state of medical knowledge. The exceptions to this standard are extremely limited and do not undermine the validity of the wider principle. Formally, the article emphasises the central role that administrative authorities conducting Health Technology Assessment (HTA) play, with delegated decisions ranging from the definition of the applicable evidentiary standards to the issuing of binding guidelines. It is argued that mechanisms must be put in place to ensure these bodies' expertise, independence, and transparency.
    Keywords:  HTA; Health technology assessment; NHS; health law; statutory health insurance
    DOI:  https://doi.org/10.1017/S1744133126100371
This page is being maintained by Thomas Krichel. It was last updated on 2026‒02‒08 at 9:33.