bims-carter Biomed News
on CAR-T Therapies
Issue of 2025–08–24
sixteen papers selected by
Luca Bolliger, lxBio
  1. Editorial: Expanding CAR-T cell therapy - breakthroughs from cancer to autoimmune diseases.
  2. Mathematical models and computational approaches in CAR-T therapeutics.
  3. Direct visualization of chimeric antigen receptors on primary human T cells using dSTORM super-resolution microscopy.
  4. CART-GPT: A T Cell-Informed AI Linguistic Framework for Interpreting Neurotoxicity and Therapeutic Outcomes in CAR-T Therapy.
  5. In vivo production of CAR T cell: Opportunities and challenges.
  6. International Consensus Guidelines for the Conduct and Reporting of CAR T-Cell Clinical Trials in AML.
  7. Adoptive cell therapy for cancer: combination strategies and biomarkers.
  8. Novel combination of irreversible electroporation and allogenic chimeric antigen receptor (CAR) T-cell therapy synergizes therapeutic outcomes in a preclinical human pancreatic cancer mouse model.
  9. Harnessing chimeric antigen receptor macrophages against solid tumors.
  10. Mapping Current Research Status and Emerging Frontiers of T-Cell Exhaustion: A Comprehensive Data-Mining-Based Study.
  11. Advances in the classification and management of idiopathic inflammatory myopathies.
  12. Global research trends on epigenetics and cancer: A bibliometric analysis.
  13. Automated, aseptic sampling with small-volume capacity from microbioreactors for cell therapy process analysis.
  14. Early-stage health technology assessment of a curative gene therapy for multiple sclerosis.
  15. CAR-T cell engineered with TCR-like antibody specific for HBV surface antigen epitope E183-91/HLA-A *0201 exhibit potent activity against HBV-HCC.
  16. Empowering single-cell analysis with emerging active microfluidic devices.
  1. Front Immunol. 2025 ;16 1649045
    Editorial: Expanding CAR-T cell therapy - breakthroughs from cancer to autoimmune diseases.
    Selene Nunez-Cruz, Yibo Yin, Jianlei Hao, Hongru Zhang.
      
    Keywords:  CAR T; CRISPR; autoimmune disease; cancer; toxicity
    DOI:  https://doi.org/10.3389/fimmu.2025.1649045
  2. Front Immunol. 2025 ;16 1581210
    Mathematical models and computational approaches in CAR-T therapeutics.
    Guido Putignano, Samuel Ruipérez-Campillo, Zhou Yuan, José Millet, Sara Guerrero-Aspizua.
       Background: The field of synthetic biology aims to engineer living organisms for specific therapeutic applications, with CAR-T cell therapy emerging as a groundbreaking approach in cancer treatment due to its potential for flexibility, specificity, predictability, and controllability. CAR-T cell therapies involve the genetic modification of T cells to target tumor-specific antigens. However, challenges persist because the limited spatio-temporal resolution in current models hinders the therapy's safety, cost-effectiveness, and overall potential, particularly for solid tumors.
    Main body: This manuscript explores how mathematical models and computational techniques can enhance CAR-T therapy design and predict therapeutic outcomes, focusing on critical factors such as antigen receptor functionality, treatment efficacy, and potential adverse effects. We examine CAR-T cell dynamics and the impact of antigen binding, addressing strategies to overcome antigen escape, cytokine release syndrome, and relapse.
    Conclusion: We propose a comprehensive framework for using these models to advance CAR-T cell therapy, bridging the gap between existing therapeutic methods and the full potential of CAR-T engineering and its clinical application.
    Keywords:  CAR-T cells; T cell engineering; biological system modeling; computational immunotherapy; mathematical modeling; synthetic biology; therapeutic optimization
    DOI:  https://doi.org/10.3389/fimmu.2025.1581210
  3. Front Immunol. 2025 ;16 1632823
    Direct visualization of chimeric antigen receptors on primary human T cells using dSTORM super-resolution microscopy.
    Leon Gehrke, Nicole Seifert, Peter Spieler, Christina Verbruggen, Rick Seifert, Fabio Toppeta, Maximilian Krick, Sören Doose, Hermann Einsele, Michael Hudecek, Markus Sauer, Thomas Nerreter.
      Chimeric antigen receptor (CAR) T cells are a transformative treatment for hematological malignancies, and concerted efforts in the field are aiming to translate this success to solid tumors and autoimmune diseases. There is a desire in the field to accurately assess CAR organization and spatiotemporal expression to elucidate mechanistic details of CAR-T cell mediated anti-tumor activity and enable evaluation of the potency and safety of CAR-T cell products. We applied an IgG4-targeted F(ab)2 to achieve direct CAR labeling for super-resolution microscopy by direct stochastic optical reconstruction microscopy (dSTORM). This enabled us to determine CAR surface expression on human primary T cells with single-molecule resolution independent of CAR specificity. We combined this direct CAR detection approach with a phenotypic assessment of the CAR-T cells, highlighting prospective applications to gain detailed mechanistic insights. With this new approach, we were able to detect the surface expression of CARs targeting SLAMF7, BCMA and CD19 with minimal background. We determined T cell subtype, donor material, and CAR construct as contributing factors shaping CAR surface expression and identified putative influence of CAR surface expression on CAR-T cell activation state. Here we provide a novel, tag-free approach to gain insights into the surface expression of CARs, illustrating the potential of super-resolution microscopy to inform the application of synthetic immune receptors for CAR-T cell therapy, potentially building the basis for more intricate and combinatorial studies to further improve the efficacy of CAR-T cell immunotherapy, predict therapeutic outcome and ensure optimal care for patients.
    Keywords:  CAR (chimeric antigen receptor); CAR-T cell; dSTORM; imaging; immunotherapy; microscopy
    DOI:  https://doi.org/10.3389/fimmu.2025.1632823
  4. bioRxiv. 2025 Aug 12. pii: 2025.08.08.669387. [Epub ahead of print]
    CART-GPT: A T Cell-Informed AI Linguistic Framework for Interpreting Neurotoxicity and Therapeutic Outcomes in CAR-T Therapy.
    Tiantian Mao, Xiaojian Shao, Wei Guo, Zhiwu Jiang, Rui Jing, Xin Li, Yiran Zhu, Tony Jin, Tao Ma, Yong Lu, Guangxu Jin.
      Chimeric antigen receptor (CAR) T cell therapy holds transformative potential for hematologic malignancies, yet predicting patient-specific treatment efficacy and neurotoxicity remains a major clinical challenge due to the complex and heterogeneous nature of the infused CAR-T cell populations. Here, we introduce CART-GPT, a transformer-based model fine-tuned on a curated atlas of 1.12 million CAR-T single-cell RNA-seq profiles annotated with clinical outcomes. CART-GPT is the first AI model developed for CAR-T therapy that predicts both treatment response and the risk of immune effector cell-associated neurotoxicity syndrome (ICANS), achieving state-of-the-art performance (AUC ~0.8) and marking a significant advance in the field. The model provides interpretable insights, revealing that neither therapeutic efficacy nor neurotoxicity is driven by individual cell types alone, but by the combined influence of discrete, distinct subsets across diverse T cell states and transcriptional programs. A novel cell aggregation strategy links single-cell predictions to patient-level metrics, enhancing both accuracy and biological relevance. As a contribution to this ever-evolving field, we also release a comprehensive, annotated single-cell CAR-T atlas as a community resource to facilitate future research in immunotherapy. These advances demonstrate the potential of foundation models in single-cell biology to inform precision CAR-T treatment planning and facilitate the rational design of next-generation cell therapies.
    DOI:  https://doi.org/10.1101/2025.08.08.669387
  5. Genes Dis. 2025 Nov;12(6): 101612
    In vivo production of CAR T cell: Opportunities and challenges.
    Zhiqiang Song, Yi Zhou, Binbin Wang, Yuke Geng, Gusheng Tang, Yang Wang, Jianmin Yang.
      Chimeric antigen receptor T (CAR T) cell therapy has achieved remarkable efficacy for patients with hematological malignancies. However, in vitro viral vector-mediated production of CAR T cells is time-consuming and expensive and impairs T cell function. On one hand, an elaborate manufacturing process not only impairs the function of CAR T cells but also limits its usage in patients with rapidly progressing diseases. On the other hand, high costs are incompatible with broad clinical applications for sizable populations. In vivo production of CAR T cells is a novel approach that can avoid complicated production processes and reduce costs through mass production. Additionally, in vivo production of CAR T cells does not damage the function of T cells compared with in vitro production. Early studies have demonstrated promising antitumor activity of in vivo CAR T cell therapy in preclinical models of hematological malignancies. In this review, we describe the latest developments of in vivo CAR T cell therapy and discuss its potential challenges for clinical application.
    Keywords:  Chimeric antigen receptor T cell; Hematological malignancies; In vivo production; Nonviral vector; Viral vector
    DOI:  https://doi.org/10.1016/j.gendis.2025.101612
  6. Blood Adv. 2025 Aug 19. pii: bloodadvances.2025017011. [Epub ahead of print]
    International Consensus Guidelines for the Conduct and Reporting of CAR T-Cell Clinical Trials in AML.
    Swati Naik, Richard Aplenc, Susanne H C Baumeister, Marco Becilli, Anand Shripad Bhagwat, Challice L Bonifant, Lihua E Budde, Christopher D Chien, Kevin J Curran, Anthony F Daniyan, Alexandra Dreyzin, Rebecca A Gardner, Sara Ghorashian, Stephen Gottschalk, LaQuisa C Hill, Mark Eric Kohler, Adam Joseph Lamble, Franco Locatelli, Maksim Mamonkin, Bilal Omer, Jae H Park, Concetta Quintarelli, Benedetta Rambaldi, Rebecca M Richards, David A Sallman, Tim Sauer, Nirali N Shah, Marion Subklewe, Corinne Summers, Sarah K Tasian, Naomi Taylor, Sarah Tettamanti, Michael R Verneris, M Paulina Velasquez, Saar I Gill.
      Early clinical experience with the use of chimeric antigen receptor (CAR)-T cell therapies for patients with acute myeloid leukemia (AML) has been beset by high rates of toxicities and low rates of response. We convened an international workshop with the goal of bringing investigators in the field of AML-directed CAR-T cell therapy together to facilitate discussion of roadblocks and to brainstorm potential solutions. Based on discussions at the workshop, it was evident (i) that treating and targeting AML with CAR-T cells is associated with unique clinical challenges, and (ii) that variability in clinical trial design, definitions of toxicities, correlative data collection, and reporting methods hinders the field's ability to compare study outcomes and to develop best practices. Further, details of fundamental CAR-T cell attributes and key correlates of efficacy and toxicity were not uniformly reported in published studies, limiting understanding of barriers to success. These observations led to a concerted team effort in which experts in basic/translational science and clinical investigation from pediatric and adult centers worked together to streamline key attributes of clinical trial design and reporting. Consensus criteria were discussed and agreed upon leading to the creation of a white paper. These guidelines aim to bolster the overall quality of AML-directed CAR-T cell research, allow for comparisons across trials and to inform the next phase of development of AML-directed CAR-T cell therapies that we hope will improve patient outcomes.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017011
  7. Front Immunol. 2025 ;16 1603792
    Adoptive cell therapy for cancer: combination strategies and biomarkers.
    Shiyu Liu, Weibo Jiang, Jiyao Sheng, Lixuan Wang, Mengying Cui.
      Adoptive cell therapy (ACT) is a therapeutic approach that involves the isolation, modification, and expansion of immune cells ex vivo, followed by their reinfusion into the patient to enhance anti-tumor immune responses. Various forms of ACT have demonstrated promising clinical outcomes across multiple types of cancer. For example, chimeric antigen receptor (CAR)-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, and T-cell receptor-engineered T cell (TCR-T) therapy have received approval from the US Food and Drug Administration. However, the clinical application of ACT remains constrained by limited efficacy and potentially life-threatening toxicities. Diminished efficacy may result from an immunosuppressive tumor microenvironment, poor trafficking and infiltration, exhaustion of infused cells, tumor heterogeneity, and antigen escape. To address these challenges, combination strategies have been developed with the goals of enhancing efficacy and managing adverse effects. Conventional treatments and non-ACT forms of immunotherapy have been incorporated into these combination approaches. Biomarkers play an essential role in optimizing ACT strategies and addressing associated complexities. They can aid in candidate selection, assess the quality of ACT products, monitor long-term therapeutic efficacy, manage toxicity, and guide combination regimens. This review briefly outlines six ACT modalities and their common limitations, summarizes current combination strategies, explores potential future regimens, and offers an overview of biomarkers relevant to ACT. These insights provide valuable guidance for the development and clinical implementation of more effective ACT-based therapies, ultimately aiming to improve patient outcomes.
    Keywords:  CAR-T cells; TCR-T cells; TILs; adoptive cell therapy; biomarkers; combination therapy; immunotherapy
    DOI:  https://doi.org/10.3389/fimmu.2025.1603792
  8. bioRxiv. 2025 Aug 12. pii: 2025.08.10.669537. [Epub ahead of print]
    Novel combination of irreversible electroporation and allogenic chimeric antigen receptor (CAR) 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 non-thermal 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 downregulated 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 an adoptive cell therapy. 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 two clinically used techniques.
    DOI:  https://doi.org/10.1101/2025.08.10.669537
  9. Cancer Commun (Lond). 2025 Aug 17.
    Harnessing chimeric antigen receptor macrophages against solid tumors.
    Mengru Wang, Zhen Qin, Xiu-Wu Bian, Yu Shi.
      Macrophages are prevalent in multiple tumors and exhibit diverse and potent functional activities. Therapeutic reprogramming of macrophage phenotypes represents a promising strategy for cancer immunotherapy. Engineering chimeric antigen receptors (CARs) to endow macrophages with anti-tumor capacities demonstrated encouraging efficacy, particularly in enhancing tumor-targeted phagocytosis. Furthermore, CAR macrophages (CAR-Ms) orchestrate adaptive immunity through secreting pro-inflammatory cytokines and presenting tumor antigens, thereby activating cytotoxic T lymphocyte responses. These multifaceted properties establish CAR-Ms as potent immunotherapeutic agents against therapy-refractory solid malignancies. Herein, we delineate the design principles, recent research advances, and rational combination strategies of CAR-Ms, with particular emphasis on emerging clinical evidence from ongoing CAR-M trials. We also explore potential applications of CAR-Ms in non-tumorous diseases and forecast future trends based on CAR-T therapy evolution. CAR-M development, combined with emerging technologies, will generate new perspectives for advancing cancer immunotherapy.
    Keywords:  chimeric antigen receptor; immunotherapy; macrophage; solid tumors
    DOI:  https://doi.org/10.1002/cac2.70053
  10. Ann Surg Oncol. 2025 Aug 18.
    Mapping Current Research Status and Emerging Frontiers of T-Cell Exhaustion: A Comprehensive Data-Mining-Based Study.
    Pengcheng Li, Qiang Guo, Yanfeng Gao, Wanqing Li, Haiyang Wu.
       BACKGROUND: T-cell exhaustion (Tex) represents a distinct immunological state characterized by the progressive functional deterioration of T cells under persistent antigenic stimulation. In recent years, the field of Tex research has attracted considerable attention, accompanied by a dramatic surge in related scientific literature. This study employed bibliometric methods to conduct a comprehensive analysis of Tex-related publications.
    METHODS: The scientific literature focusing on Tex published between 2005 and 2024 was retrieved from the Web of Science Core Collection. For comprehensive bibliometric evaluation, tools including CiteSpace, VOSviewer, and online websites were used to construct visual networks, including co-authorship, co-citation, and co-occurrence analysis. Quantitative assessment of research output and impact was performed through multiple metrics.
    RESULTS: The analysis included a total of 2831 publications. The data fitting analysis indicated an exponential growth in the number of publications per year. Regarding research contributions, the United States and China have consistently demonstrated their leading positions. Among academic institutions and individual researchers, Harvard University has emerged as the most productive organization. Reference analysis showed that chimeric antigen receptor (CAR) T-cell therapy is one of the fields that attract greatest attention in the current Tex research. Keyword analysis revealed that cancer was the most studied disease in this area, followed by hepatocellular carcinoma and HIV. Analysis of high-frequency keywords also found that current research focuses on the field centered around immunotherapy and immune checkpoint inhibitors, functional status of T cells and the mechanisms underlying Tex, tumor microenvironment, prognosis and biomarkers, and the role of Tex in specific diseases. In addition, in the coming years, several key areas will remain at the forefront of scientific exploration. These include machine learning, pan-cancer, programmed death-1 blockade, scRNA-seq, immune tolerance, VISTA, immunotherapy resistance, exosome, chronic inflammation, gene editing, triple-negative breast cancer, tumor microenvironment, solid tumors, multiple myeloma, and extracellular vesicles.
    CONCLUSIONS: This research represents the inaugural effort to perform an extensive bibliometric evaluation of literature focusing on Tex between 2005 and 2024. The findings derived from this analysis offer a credible resource for scholars aiming to swiftly grasp essential insights and emerging trends, as well as future hotspots within this domain.
    Keywords:  Bibliometrics; Data mining; Research hotspots; Research status; T-cell exhaustion
    DOI:  https://doi.org/10.1245/s10434-025-18066-2
  11. Lancet Neurol. 2025 Sep;pii: S1474-4422(25)00233-9. [Epub ahead of print]24(9): 776-788
    Advances in the classification and management of idiopathic inflammatory myopathies.
    Joost Raaphorst, Anneke J van der Kooi, Christopher A Mecoli, Conrad C Weihl, Sander W Tas, Jens Schmidt, Marianne de Visser.
      Idiopathic inflammatory myopathies are a group of immune-mediated disorders characterised by multisystem involvement and a chronic disease course in two-thirds of adult patients. Autoantibodies can aid in the identification of disease subtypes and their associated severe complications, such as cancer or interstitial lung disease. Patients with idiopathic inflammatory myopathies need to be managed in a multidisciplinary setting. Treatment with intravenous immunoglobulins is efficacious in patients with refractory dermatomyositis, and can result in improvements in disease activity in the skin and muscle. Numerous randomised controlled trials are underway testing potential therapeutic agents that hold promise for the treatment of idiopathic inflammatory myopathies. Other advances include the identification of pathophysiological mechanisms. Induction of interferons in patients with dermatomyositis leads to the upregulation of interferon-stimulated genes in blood, skin, and muscle tissue. The interferon-induced transcripts could yield diagnostic biomarkers and biomarkers for monitoring disease activity. The identification of these potential biomarkers has also propelled the development of therapies targeting the interferon pathway-either upstream by using monoclonal autoantibodies or by blocking downstream signalling pathways via JAK inhibitors. A promising strategy for patients with refractory disease is targeting B cells with CD19-targeting chimeric antigen receptor T-cell therapy. Treatments targeting T cell lymphocytes and specific T-cell subsets are also under investigation.
    DOI:  https://doi.org/10.1016/S1474-4422(25)00233-9
  12. Medicine (Baltimore). 2025 Aug 15. 104(33): e43197
    Global research trends on epigenetics and cancer: A bibliometric analysis.
    Xinyi Zhong, Du Chen.
       BACKGROUND: Epigenetics in cancer has been a focus of intense research in the recent years. This phenomenon has attracted great interest because it offers potential targets for cancer therapy. To capture the intellectual landscape of this field, this article conducted a bibliometric analysis to assess the current status, frontiers and future trends of epigenetic research in cancers.
    METHODS: A bibliometric analysis was performed using data from the Web of Science Core Collection up to 2023. Analytical tools such as CiteSpace, VOSviewer, and the R package "bibliometrix" were employed for comprehensive data analysis and visualization. This process identified the publication of the articles, countries, authors, institutions, journals and keywords.
    RESULTS: The results showed that there were 51,742 articles from the WoSCC database during 1985 to 2023 for cancer epigenetics. The number of epigenetic cancer-related publications has increased annually. The most contributed country is the United States, with 850,726 citations and 55 average article citations. China ranks second, with 413,386 citations and an average of 44.7. The most productive institutions were from the USA. Plos One (1020), International Journal of Molecular Sciences (957), and Cancers (945) were the top 3 contributing journals. The top 3 most common keywords were "DNA methylation," "expression" and "cancer." Research hotspots within these themes highlight intensive areas of study and the potential for significant breakthroughs.
    CONCLUSIONS: This study presents an in-depth overview of the current state of epigenetics in cancers research. And the purpose of this review will be to understand the characteristics of bibliometric analyses of epigenetic cancers and anticipate the progress in understanding this field.
    Keywords:  VOSviewer; bibliometrics; cancer; citespace; epigenetic
    DOI:  https://doi.org/10.1097/MD.0000000000043197
  13. Front Bioeng Biotechnol. 2025 ;13 1612648
    Automated, aseptic sampling with small-volume capacity from microbioreactors for cell therapy process analysis.
    Zhi Xian Chan, Shruthi Pandi Chelvam, Wei-Xiang Sin, Denise Bei Lin Teo, Ahmad Amirul Bin Abdul Rahim, Ying Ying Wu, Dan Liu, Michael E Birnbaum, Derrick Yong, Rajeev J Ram.
      Current workflows in autologous cell therapy manufacturing are reliant on manual processes that are difficult to scale out to meet patient demands. High throughput bioreactor systems that enable multiple cultures to occur in parallel can address this need, but require good bioprocess monitoring workflows to produce good quality cell therapy products. Commercial sampling systems have thus been developed for better feedback control and monitoring capabilities. However, they are targeted towards large scale processes and often bioreactor specific, making them less robust for integration across different bioreactor scales and types, such as perfusion-capable microbioreactors which allows for greater process intensification. Here, an automated cell culture sampling system (Auto-CeSS) was developed to eliminate laborious manual sampling while minimizing sterility risks for cell therapy manufacturing processes. The system is aseptically integrated with a variety of bioreactors of different working volumes. This system can accurately and aseptically sample a minimum volume of 30 μL and can consistently perform periodic sampling of supernatant over a minimum interval of 15 min. We integrated Auto-CeSS with a 2 mL perfusion microbioreactor and a 8 mL gas-permeable well-plate for T cell culture, collecting 200 μL of supernatant samples daily for metabolite analysis. Comparison of the metabolic profiles of the samples collected via Auto-CeSS versus manual sampling revealed insignificant differences in metabolite levels, including glucose, lactate, glutamine, and glutamate. This report demonstrates the potential of Auto-CeSS as an at-line sampling platform in a real-time T cell production run to facilitate in-process culture monitoring.
    Keywords:  aseptic; autosampler; bioreactor; car-t; microbioreactor; sampling; small-volume
    DOI:  https://doi.org/10.3389/fbioe.2025.1612648
  14. Br J Clin Pharmacol. 2025 Aug 18.
    Early-stage health technology assessment of a curative gene therapy for multiple sclerosis.
    Attila Imre, Balázs Nagy, Rok Hren.
       AIMS: Multiple sclerosis (MS) is associated with significant early morbidity, reduced life expectancy and substantial healthcare and societal costs. The primary objective of this study is to assess the early cost-effectiveness potential of a novel gene therapy, IMMUTOL, for MS compared with current high-efficacy treatment sequences. The secondary objective is to explore value-based pricing thresholds in line with Dutch health economic guidelines.
    METHODS: Using the ErasmusMC/iMTA MS microsimulation model, we compared IMMUTOL gene therapy against various high-efficacy and escalation-based disease-modifying therapy sequences. Analyses considered a lifetime horizon, societal and healthcare perspectives, and uncertainty through probabilistic sensitivity analysis. The IMMUTOL gene therapy scenarios varied in efficacy parameters (relapse and disability reduction) and adverse event profiles. Cost assumptions incorporated projected market dynamics, including future price reductions due to generics and biosimilars.
    RESULTS: IMMUTOL gene therapy demonstrated dominance (higher quality-adjusted life years, lower costs) at price points ≤€200 000 and remained cost-effective at €500 000 under realistic clinical scenarios (incremental cost-effectiveness ratio €26 570-€40 615/quality-adjusted life year). Its cost-effectiveness threshold depended on sustained reductions in relapse rates and disability progression (incidence rate ratio ≤0.2, relative risk ≤0.1). Indirect societal costs improved gene therapy's economic attractiveness.
    CONCLUSIONS: IMMUTOL gene therapy shows promising cost-effectiveness at a value-based price up to approximately €500 000, contingent on achieving curative clinical efficacy. These findings inform strategic development and pricing considerations for emerging gene therapies in MS.
    Keywords:  gene therapy; health economics; modelling and simulation; multiple sclerosis; pharmacoeconomics
    DOI:  https://doi.org/10.1002/bcp.70204
  15. Oncoimmunology. 2025 Dec;14(1): 2546404
    CAR-T cell engineered with TCR-like antibody specific for HBV surface antigen epitope E183-91/HLA-A *0201 exhibit potent activity against HBV-HCC.
    Fengling Wang, Jiaqian Li, Yong Huang, Feiyang Yan, Haozhan Gao, Weilin Zhou, Xinyu Gu, Dan Li, Yalan Zhang, Jing Li, Yuening Yang, Jiangping Yang, Mengxi Zhang, Jinrong Yang, Shimao Qi, Wei Wang.
      CAR-T cell therapy demonstrates significant efficacy in hematologic malignancies, with target selection critically determining therapeutic outcomes. However, the available tumor surface antigens are limited, especially in the treatment of solid tumors. A potential solution to overcome this limitation entails employing antibodies recognizing peptide-major histocompatibility complex (pMHC) structures, enabling CAR-T cell to detect intracellular tumor antigens through a T cell receptor (TCR)-like recognition mechanism. This study focuses on HBV-associated hepatocellular carcinoma (HBV-HCC), where HBV DNA integration into the host genome generates specific viral antigen epitopes presented by MHC class I molecules, representing attractive targets for CAR-T cell therapy. We engineered CAR-T cells with a TCR-like antibody (HBs183 CAR-T) specific for the immunodominant HBV envelope epitope Env183-191 presented by HLA-A *0201, and evaluated the antigen-specific cytotoxicity and safety profile of the CAR-T cells through in vitro functional assays and in vivo evaluation in heterogenous tumor models (subcutaneous and intraperitoneal xenografts). Our research provides a reference for CAR-T cell therapy targeting intracellular antigens, particularly specific antigens derived from viral infections, as targets for CAR-T treatment, and offers a preliminary concept validation for the CAR-T treatment of HBV-HCC tumors.
    Keywords:  Chimeric antigen receptor; Env183-191 epitope; HBV-HCC; MHC; TCR-like antibody
    DOI:  https://doi.org/10.1080/2162402X.2025.2546404
  16. Biomaterials. 2025 Aug 08. pii: S0142-9612(25)00536-8. [Epub ahead of print]325 123617
    Empowering single-cell analysis with emerging active microfluidic devices.
    Qingyu Ruan, Wenshang Guo, Ruizhe Yang, Tie Sun, Qisheng Yang, Yukun Ren.
      Understanding cellular heterogeneity is crucial for deciphering infection mechanisms, disease progression, and identifying novel biomarkers for personalized therapies, which provides valuable insights into biological processes and supports decision-making in biomedical settings. Microfluidics is a compact and lightweight system that enables efficient, high-throughput single-cell isolation and real-time analysis, making it the prevailing technology for single-cell analysis. Despite the advantages, microfluidic methods face several limitations, such as the need for off-chip pretreatment and post-processing, poor cell manipulation, and high cell damage, which hinder their broader application. Active microfluidics, which combines electrical, magnetic, acoustic, and optical technologies with microfluidic platforms, addresses some of these issues by creating a controlled microenvironment that enables precise, non-invasive, and high-throughput single-cell analysis. This review summarizes the latest advances in active microfluidics for applications, including nucleic acid, protein, cellular, and omic analysis. We also discuss the pros and cons of these technologies, offering guidance for researchers in selecting appropriate methods for desired single-cell analysis. Finally, we critically examine the current limitations of active microfluidic single-cell workflows and propose potential solutions to overcome these challenges.
    Keywords:  Active microfluidics; Dielectrophoresis; Digital microfluidics; Lab-on-a-chip; Single cells
    DOI:  https://doi.org/10.1016/j.biomaterials.2025.123617
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