bims-carter Biomed News
on CAR-T Therapies
Issue of 2026–02–15
43 papers selected by
Luca Bolliger, lxBio



  1. Ann Med. 2026 Dec;58(1): 2627057
       BACKGROUND: Chimeric antigen receptor (CAR) -T cell therapy has emerged as a promising approach for treating severe autoimmune diseases (AIDs), offering distinct advantages over conventional immunosuppressive therapies. This review examines recent advancements in both autologous and allogeneic CAR-T platforms for AIDs.
    METHODS: We analyzed preclinical and clinical evidence regarding CAR-T therapies. These therapies target signaling molecules across various cells in the myeloid and lymphoid lineages, addressing autoimmune pathologies across dermatological, neurological, gastrointestinal, and hematological systems.
    RESULTS: Diversified CAR-T technological innovations have been developed. CAR-T therapy achieves remarkable efficacy in various AID by precisely eliminating pathogenic cells and facilitating a systemic immune reset, thereby maintaining a favorable balance between therapeutic benefit and safety.
    CONCLUSION: CAR-T cell therapy represents a revolutionary therapeutic strategy for the management of refractory AIDs. Addressing current challenges will further promote its clinical translation and expand its application in the treatment of AIDs.
    Keywords:  CAR-T cell therapy; RA; SLE; SSc; autoimmune diseases; pemphigus
    DOI:  https://doi.org/10.1080/07853890.2026.2627057
  2. Int J Mol Sci. 2026 Jan 28. pii: 1292. [Epub ahead of print]27(3):
      Chimeric antigen receptor (CAR)-engineered immune cell therapies have revolutionized cancer treatment, with CAR-T cells demonstrating remarkable efficacy against hematological malignancies. However, the effectiveness of CAR-T and other lymphocyte-based therapies against solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment and poor infiltration of effector cells. Recently, CAR-macrophage (CAR-M) immunotherapy has emerged as a promising strategy to overcome these barriers. Leveraging the innate tumor-homing ability, phagocytic function, and antigen-presenting capacity of macrophages, CAR-M therapies offer unique advantages for targeting solid tumors. This review provides a comprehensive overview of the development and current state of CAR-Macrophage immunotherapy, including advances in CAR design and macrophage engineering, preclinical and clinical progress, and mechanistic insights into their anti-tumor activity. The review critically examined both the benefits and limitations of CAR-M approaches, addressing persistent challenges such as cell sourcing, durability, and safety, while also exploring innovative strategies to enhance therapeutic efficacy. Finally, future perspectives and the potential clinical impact of CAR-macrophage therapies were outlined, underscoring their emerging role in the evolving landscape of cancer immunotherapy.
    Keywords:  cancer; cell therapy engineering; chimeric antigen receptor; immunotherapy; macrophages; solid tumors; tumor microenvironment
    DOI:  https://doi.org/10.3390/ijms27031292
  3. J Vis Exp. 2026 Jan 23.
      Engineering multiple receptors into chimeric antigen receptor (CAR) T cells has emerged as a powerful strategy to prevent antigen-negative relapse and reduce on-target/off-tumor toxicities. However, manufacturing multi-receptor CAR T cells remains challenging, as increasing lentiviral transgene sizes significantly reduces viral titers and T cell transduction rates. Current production workflows often rely on cell sorting to enrich transduced T cells from low-yield productions. Yet, cell sorting techniques do not increase the absolute number of CAR T cells and add further complexity to the already elaborate manufacturing process. Consequently, these limitations impede the clinical translation of multi-receptor CAR T cells and restrict the development of next-generation immunotherapies. Here, we present a detailed, step-by-step production workflow optimized for generating CAR T cells with large lentiviral transgenes. Using this workflow, we demonstrate size-dependent increases in transduction efficiency across a range of transgene sizes, with the most pronounced enhancement of up to 14.8-fold observed for a 10.1 kb lentiviral vector. Importantly, the workflow supports robust T cell expansion and eliminates the need for cell sorting. By overcoming current size limitations in lentiviral gene transfer, this workflow enables the efficient generation of multi-receptor CAR T cells, thereby facilitating the development of advanced immunotherapies.
    DOI:  https://doi.org/10.3791/69121
  4. Cancer Treat Res Commun. 2026 Jan 30. pii: S2468-2942(26)00036-5. [Epub ahead of print]47 101125
      Chimeric Antigen Receptor T-cell (CAR-T cell) therapy is a promising cancer treatment that has shown success in treating certain type of cancer. It has demonstrated remarkable efficacy, particularly in hematologic malignancies such as certain types of leukemia and lymphomas, offering hope for patients with limited options. In this review the authors highlighted the importance of CAR-T cell therapy in oncology, history, recent innovations in CAR-T cell engineering and development, mechanism of action, toxic effects, clinical trials and ongoing research on CAR-T cell therapy. Barriers to effective CAR-T cell therapy includes antigen escape, tumor heterogeneity, microenvironment of the tumor, On target, Off tumor toxicity, modest anti-tumor activity and limited tumor infiltration. In this review we discussed global regulations of CAR-T cell therapies, challenges of harmonized regulations, FDA approved CAR-T cell therapies, clinical applications, clinical trials and research and future prospects of CAR-T cell therapy.
    Keywords:  Antigens; CAR-T cells; Cancer; Immunotherapy; Personalized treatment
    DOI:  https://doi.org/10.1016/j.ctarc.2026.101125
  5. Crit Rev Oncol Hematol. 2026 Feb 10. pii: S1040-8428(26)00096-X. [Epub ahead of print] 105209
      Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematological malignancies but remains constrained by complex, individualized ex vivo manufacturing, limiting its accessibility and scalability. Direct in vivo generation of CAR-T cells within the patient offers a transformative approach to overcome these bottlenecks. However, the viral vector systems that enable this process have received comparatively limited attention in existing literature, where most reviews emphasize non-viral technologies. This review focuses on viral vectors as the pivotal enablers of in vivo CAR-T therapy. We summarize major directions in vector innovation, including engineering strategies to enhance tropism and safety, clinical applications across diverse disease settings, and the intrinsic trade-offs that shape translational outcomes. Current challenges are considered in the context of emerging technologies designed to improve precision, controllability, and clinical feasibility. By integrating these perspectives, this review outlines how viral vector-mediated in vivo CAR-T platforms may evolve toward more accessible, programmable, and safer next-generation cell therapies.
    Keywords:  T cell; chimeric antigen receptor; immunotherapy; virus
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105209
  6. Cancer Cell. 2026 Feb 12. pii: S1535-6108(26)00056-5. [Epub ahead of print]
      In this issue of Cancer Cell, Rade et al. report a longitudinal single-cell atlas of multiple myeloma patients receiving BCMA-directed chimeric antigen receptor (CAR) T cell therapy (ide-cel or cilta-cel) and identifiy features linked to long-term responses, including CD4+ T cell-driven cytotoxicity, memory-biased T cell states, reduced exhaustion, and microenvironment effects.
    DOI:  https://doi.org/10.1016/j.ccell.2026.01.017
  7. Nano Lett. 2026 Feb 11.
      CAR T cell therapy represents a leading therapeutic modality in the treatment of hematological cancers. However, conventional ex vivo manufacturing processes are extremely complex, costly, and time-consuming. Hence, in vivo CAR-T cell therapy represents a promising alternative, where T cells are genetically modified directly within the patient. This novel approach requires the careful design of three modular and interdependent nanoscale parameters: CAR architecture, targeted lipid nanoparticle delivery systems, and nucleic acid cargo format. Each component is highly modular, therefore systematic optimization can enhance the safety and efficacy of in vivo CAR T cell generation. Here, we review the molecular and mechanistic principles underlying this therapeutic strategy, emphasizing how these nanoscale design features govern CAR T cell production and functional performance in vivo. Advancing our understanding of these parameters is critical to developing efficient, safe, and clinically translatable in vivo CAR T cell cancer therapies.
    Keywords:  CAR T cells; drug targeting; lipid nanoparticles; nanomedicine; nucleic acid therapeutics
    DOI:  https://doi.org/10.1021/acs.nanolett.5c05535
  8. Clin Cancer Res. 2026 Feb 09.
      Most patients with solid tumors either never benefit from immune checkpoint inhibitors (ICIs) or relapse after an initial response, underscoring the need for additional therapies. Clinical and translational evidence points to two complementary strategies to overcome ICI resistance: redirection of effector cells by imposing novel tumor-specificity via engineered T cell receptors (TCRs), chimeric antigen receptors (CARs), and CD3/TCR engagers, and augmentation of endogenous responses by tumor infiltrating lymphocyte (TIL) therapy, cytokine support, and microenvironment remodeling. This review integrates emerging signals across platforms and examines why some designs succeed while others stall. Therapeutic efficacy depends on tumor target features and the surrounding microenvironment. Clinical efficacy is emerging when (i) tumor targets show high density and uniformity with restriction to malignant cells, (ii) antigen presentation can be harnessed for TCR-based strategies or bypassed with CARs and engagers, and (iii) the tumor contexture is permissive or convertible with regional delivery and stromal, vascular, or myeloid modulation. Engineering solutions such as tuned costimulation, cytokine armoring, and resistance to suppression improve effector expansion and persistence. Safe and scalable delivery requires exposure control and operational solutions in manufacturing and logistics. Step-up dosing and optimized routes can limit peak exposure and resource intensity. Autologous manufacturing and time to treatment remain limiting, whereas off-the-shelf platforms improve logistics. For patients, near-term progress will rely on biomarker-guided selection and pragmatic trials that address sequencing and bridging, while benchmarking durability across modalities.
    DOI:  https://doi.org/10.1158/1078-0432.CCR-24-3694
  9. Transl Cancer Res. 2026 Jan 31. 15(1): 2
      
    Keywords:  CRISPR knock-in; Chimeric antigen receptor T cells (CAR T cells); solid tumors; tumor-restricted promoters
    DOI:  https://doi.org/10.21037/tcr-2025-aw-2291
  10. Acta Biochim Biophys Sin (Shanghai). 2026 Feb 11.
      Chimeric antigen receptor T (CAR-T) cell therapy achieves remarkable success in hematological cancers, but its efficacy is severely limited in solid tumors by formidable obstacles including physical barriers, the highly immunosuppressive tumor microenvironment (TME), and antigen escape. To address these persistent challenges, chimeric antigen receptor-macrophage (CAR-M) therapy emerges as a promising alternative, leveraging intrinsic advantages of macrophages like unparalleled tumor infiltration, powerful phagocytosis, and high plasticity. The evolution of CAR-M is primarily defined by the intracellular signaling domain. CAR-M exerts its anti-tumor effects through multifaceted mechanisms, including direct enhanced phagocytosis and tumor cell killing, TME remodeling by repolarizing to a pro-inflammatory M1-like phenotype, releasing anti-tumor effectors, and degrading the extracellular matrix (ECM), and the activation of adaptive immunity via efficient antigen presentation. Despite its promise, CAR-M faces hurdles such as TME physical barriers and the potential for M2-like re-education. Current optimization strategies focus on enhancing tumor infiltration, overcoming immunosuppression with "armored" CAR-Ms, and improving safety with suicide switches. Encouraging pre-clinical data accelerates CAR-M into early-phase clinical trials for solid tumors, and the platform's utility is also being explored beyond oncology in infectious, autoimmune, and neurodegenerative diseases.
    Keywords:  CAR-macrophages (CAR-Ms); adoptive cell therapy; solid tumors; tumor microenvironment remodeling
    DOI:  https://doi.org/10.3724/abbs.2026017
  11. Mol Ther. 2026 Feb 06. pii: S1525-0016(26)00092-4. [Epub ahead of print]
      CAR T cell therapies achieved remarkable and durable clinical responses in several hematologic malignancies, yet their broader impact remains limited by toxicities and reduced efficacy, especially in solid tumors. Building on the successes and limitations of approved CAR therapies, more than 1,800 clinical trials were registered over the past decade. As of September 2025, 33% investigate next-generation CAR T products that incorporate auxiliary features intended to enhance safety and therapeutic efficacy (multifunctional CAR T cells). In this systematic review, we screened such multifunctional approaches across the complete landscape of CAR T cell trials registered at Clinicaltrials.gov. To provide a comprehensive discussion of this emerging paradigm and better understand its real-world impact, we classified multifunctional CAR trials as either safety- or efficacy-enhancements and monitored their registration frequency over the past twenty years. We describe each type of multifunctional CAR T cell currently present in clinical trials and discuss their subtypes, pervasiveness, alongside the clinical results thus far available. Taken together, our mapping highlights three main developments: efficacy enhancements have advanced more rapidly than safety strategies both in number and diversity; multi-targeting approaches have gained momentum; and combined strategies that simultaneously incorporate safety and efficacy enhancements are emerging to bridge individual shortcomings.
    DOI:  https://doi.org/10.1016/j.ymthe.2026.02.006
  12. J Exp Med. 2026 Mar 02. pii: e20252289. [Epub ahead of print]223(3):
      Cancer immunotherapy has mostly relied on conventional T cells to achieve success in a limited set of tumor types. A promising avenue to expand the repertoire of cancers effectively treated through immune intervention is to mobilize other anti-tumor effectors, such as γδ T cells. Among these, the Vδ1+ subset commonly predominates within peripheral tissues and within tumors, typically associating with good prognosis. In this Found in Translation, we discuss how to leverage the biological properties of Vδ1+ γδ T cells for cancer immunotherapy, with special focus on the delta one T (DOT) cell approach.
    DOI:  https://doi.org/10.1084/jem.20252289
  13. Res Sq. 2026 Feb 02. pii: rs.3.rs-8704178. [Epub ahead of print]
      γδ T cell-based immunotherapies have gained relevance as an alternative to the conventional αβ T cell products with pre-clinical data demonstrating tumor burden reduction and mitigation of tumor-induced damage. Given that most CAR constructs were optimized for αβ T cells, we hypothesized that distinct T cell types may require tailored CAR architectures to achieve optimal function. To test this hypothesis, we conducted a systematic comparative analysis between γδ and αβ T cells transduced with a second-generation PSCA-targeting CAR (PSCA-8t28z). We found that although γδ and αβ CAR-T cells exhibit comparable cytotoxicity, they differ phenotypically. Through a system level phosphoproteomic analysis, we identified 307 phospho-sites with differential abundance between γδ and αβ CAR-T cells. Pathway enrichment analysis placed glycolysis/gluconeogenesis and TCR signaling within the top significantly overrepresented signaling networks. Functional validation studies confirmed that γδ CAR-T cells show lower glycolytic and oxidative phosphorylation capacity than αβ, and weaker Activator Protein 1 (AP-1) activation. Notably, we identified Thioredoxin-Interacting Protein as a potential actionable target to enhance γδ CAR-T cell metabolism. Finally, we designed a new synthetic co-stimulatory receptor that potentiates AP-1 activation resulting in improved in-vivo persistence. These results highlight fundamental biological differences between γδ and αβ T cells and support the development of cell type-specific receptor engineering strategies to maximize γδ CAR-T cell function and therapeutic benefit.
    DOI:  https://doi.org/10.21203/rs.3.rs-8704178/v1
  14. J Nanobiotechnology. 2026 Feb 11. 24(1): 159
      Exosomes are nanoscale extracellular vesicles that transfer proteins, nucleic acids, and lipids, reflecting the state of their parent cells. A persistent scientific challenge is that tumor-derived exosomes (TDEs) facilitate immune evasion, remodel the tumor microenvironment, and create premetastatic niches, intensifying tumor aggressiveness and undermining therapeutic efficacy, ultimately narrowing treatment options to palliative strategies in advanced settings. Yet their dual roles as suppressive agents and potential therapeutic tools remain poorly integrated within current cancer immunotherapy frameworks. This review examines the molecular mechanisms underlying TDE-mediated immune suppression and therapeutic resistance, while also highlighting engineering strategies to exploit or counteract exosome biology. Exosomes derived from chimeric antigen receptor (CAR) T cells preserve antigen specificity and cytotoxic components without the risks of uncontrolled proliferation or cytokine release, offering a safer class of cell free immunotherapies. Advances in genetic engineering, hybrid vesicle design, and nanotechnology have extended exosome applications to the delivery of CRISPR/Cas systems, chemotherapeutic agents, immunoregulatory RNAs, and vaccines, with liposome or nanoparticle integration enhancing targeting and efficacy. Remaining obstacles include the lack of standardized protocols, scalability issues in production, and unresolved regulatory frameworks. Drawing on The Art of War, exosomes can be envisioned as avatars of strategy, discreet messengers capable of undermining host defenses while simultaneously carrying the potential to redirect immunity against the tumor. By embodying both deception and counterattack, they illustrate the capacity to penetrate hidden barriers and redefine the therapeutic battlefield, opening new horizons for precision cancer immunotherapy.
    Keywords:  CAR-T exosomes; CRISPR/Cas9 delivery; Cancer resistance; Cell-free therapy; Chimeric antigen receptor (CAR) t cells; Drug delivery; Exosome engineering; Exosomes; Extracellular vesicles (EVs); Immune suppression; Immunotherapy; Nanotechnology; Pre-metastatic niche; Tumor microenvironment (TME); Tumor-derived exosomes (TDEs)
    DOI:  https://doi.org/10.1186/s12951-026-04089-8
  15. Res Sq. 2026 Feb 04. pii: rs.3.rs-8436008. [Epub ahead of print]
      Some patients cannot receive T cell therapies because their cells are unable to be manufactured. To address this limitation, we developed K562-based artificial antigen-presenting cells (aAPCs) expressing an OKT3-derived scFv for TCR stimulation, CD86 and 4-1BBL for costimulation, and membrane-bound IL-7 and IL-15Rα/IL-15 for cytokine support. From these aAPCs, we generated cell-derived nanoparticles (CDNPs) that accelerated T cell entry into the cell cycle compared with CD3/28-coated beads, enabling efficient concurrent activation and lentiviral transduction. CDNPs robustly expanded T cells from patients whose products could not be manufactured using standard approaches, and these CDNP-derived CAR T cells controlled tumors in humanized mouse models. In a phase I trial of patients with CD19⁺ malignancies (NCT04684563), cGMP-compatible CDNPs enabled streamlined 3-day manufacturing of IL-18-expressing CD19 CAR T cells, yielding higher cell recovery and durable clinical responses without unexpected toxicities, supporting CDNPs as a platform for commercial CAR T cell production.
    DOI:  https://doi.org/10.21203/rs.3.rs-8436008/v1
  16. Int J Hematol. 2026 Feb 08.
      Graft-versus-host disease (GVHD) remains a major barrier to successful allogeneic hematopoietic stem cell transplantation, and its prevention requires not only suppression of early alloimmune responses but also the rational design of post-transplant immune reconstitution. The pathophysiology of GVHD has traditionally been understood based on Billingham's classical three criteria and a subsequent cytokine storm-driven, multistep model that emphasizes early tissue injury. In recent years, however, emerging concepts-including disruption of tissue tolerance in target organs and the layered reconstitution of donor T cells after transplantation, characterized by dynamic changes in fitness and exhaustion-have led to a refinement of these classical frameworks. This review summarizes recent advances, focusing on two key aspects: (1) updated local pathophysiological mechanisms, including injury to tissue stem cells and impaired regenerative capacity in target organs, disruption of the gut microbiota-metabolic network, and damage to the bone marrow hematopoietic niche; and (2) the mechanistic links between immune reconstitution and the development of acute and chronic GVHD, based on recent studies of donor T cell clonal dynamics. These insights support a shift from a unidimensional, immunosuppression-centered approach toward a novel, multidimensional therapeutic strategy that integrates organ protection, hematopoietic niche repair, and precise control of immune reconstitution.
    Keywords:  Allogeneic hematopoietic stem cell transplantation; Graft-versus-host disease; Immune reconstitution
    DOI:  https://doi.org/10.1007/s12185-026-04176-4
  17. Zhonghua Xue Ye Xue Za Zhi. 2026 Jan 14. 47(1): 90-95
      Acute graft-versus-host disease (aGVHD) remains a severe complication following allogeneic hematopoietic stem cell transplantation, and traditional corticosteroid therapy often demonstrates limited efficacy. This review highlights the recent advances in cellular and targeted immunotherapies for aGVHD. Mesenchymal stem cells show considerable efficacy in steroid-resistant aGVHD and are already in clinical use. Regulatory T cells (Treg), including CAR-engineered Tregs, effectively induce immune tolerance and reduce GVHD incidence. Targeted agents, such as CTLA-4 fusion proteins and α4β7 integrin antibodies, mitigate severe aGVHD by blocking immune activation or T-cell homing. Additionally, tissue-repair factors (e.g., IL-22, GLP-2 analogs) and immunomodulatory molecules (e.g., α1-antitrypsin) offer novel strategies that combine tissue protection with immunomodulation. Collectively, these innovative therapies are driving aGVHD treatment toward precision, high efficacy, and low toxicity, demonstrating a promising clinical potential.
    DOI:  https://doi.org/10.3760/cma.j.cn121090-20250717-00338
  18. Proc Natl Acad Sci U S A. 2026 Feb 17. 123(7): e2530977123
      Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8+ cells, CD4+ T cells capable of regulating inflammation show promise in reducing pathology and improving cognitive outcomes in mouse models of AD and in aging. Here, we sought to exploit the beneficial properties of CD4+ T cells while circumventing the need for TCR and peptide-MHC antigen discovery, thereby providing a potential universal therapeutic approach. To achieve this, we engineered CD4+ T cells with chimeric antigen receptors (CARs) targeting fibrillar forms of aggregated amyloid-β. Our findings demonstrate that optimized CAR-T cells can alter amyloid deposition in the dura and reduce parenchymal pathology in the brain. Furthermore, we observed that CAR-T treatment promotes the expansion and recruitment of endogenous CD4+ T cells into the brain parenchyma and leptomeninges. In summary, we established the feasibility of amyloid plaque-specific CAR-T cells as a potential therapeutic avenue for AD. These findings highlight the potential of CD4+ CAR-T therapy not only to modify amyloid pathology but also to reshape the immune landscape of the CNS, paving the way for future development of cellular immunotherapies for neurodegenerative disease.
    Keywords:  Alzheimer’s disease; CAR T cells; T cell; chimeric antigen receptors; neurodegeneration
    DOI:  https://doi.org/10.1073/pnas.2530977123
  19. Immunity. 2026 Feb 10. pii: S1074-7613(26)00044-0. [Epub ahead of print]59(2): 238-240
      Defining the antigen specificity of T cell receptors (TCRs) remains a significant barrier to understanding adaptive immunity in various pathologies. In this issue of Immunity, Gaglione et al. report the development of TCRAFT, a novel platform that enables facile construction of vast TCR sequence libraries that can be screened against hundreds of antigens. This approach makes functional immune screening highly accessible.
    DOI:  https://doi.org/10.1016/j.immuni.2026.01.024
  20. Cureus. 2026 Jan;18(1): e101121
       BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the management of hematologic malignancies but is associated with significant toxicities, including opportunistic infections such as cytomegalovirus (CMV). Limited evidence exists regarding the clinical impact of CMV in CAR-T recipients. This study evaluated outcomes associated with CMV infection in this population.
    METHODS: A retrospective cohort study was conducted using the 2021 Healthcare Cost and Utilization Project-National Readmissions Database (HCUP-NRD). Adult patients hospitalized for CAR-T therapy for multiple myeloma, non-Hodgkin lymphoma, or acute leukemia were included. Propensity score matching was applied to balance baseline characteristics, and weighted analyses were conducted in R software (R Foundation for Statistical Computing, Vienna, Austria) to compare outcomes between CMV-positive and CMV-negative groups.
    RESULTS: Among 1,806 hospitalizations, CMV infection was identified in 2.2% of patients during the index admission. In the matched cohort, in-hospital mortality in the CMV group compared with non-CMV patients (10.3% vs. 2.6%; risk ratio (RR) 3.9, 95% CI: 0.46-33.3; p = 0.36). CMV infection was associated with significantly longer length of stay (41.5 vs. 15.9 days; adjusted ratio 1.67, 95% CI: 1.27-2.19; p < 0.01) and increased risk of encephalopathy (RR 13.21, 95% CI: 1.66-105.2; p = 0.015). Other complications, including cytokine release syndrome, tumor lysis syndrome, acute kidney injury, and transfusion requirements, did not differ significantly. At three months post-CAR-T, the cumulative incidence of patients hospitalized with CMV infection was 4.2%. Three-month mortality was significantly higher in CMV patients compared with non-CMV patients (15.8% vs. 2.5%; RR 6.32, 95% CI: 1.46-27.3; p = 0.004).
    CONCLUSION: CMV infection in CAR-T recipients is associated with increased in-hospital mortality, extended hospital stays, and a higher risk of encephalopathy. These findings underscore the importance of vigilant monitoring and early management of CMV in this high-risk population.
    Keywords:  chimeric antigen receptor (car) t-cell; cytomegalovirus (cmv); incidence; length of hospital stay (los); mortality
    DOI:  https://doi.org/10.7759/cureus.101121
  21. Methods. 2026 Feb 11. pii: S1046-2023(26)00014-9. [Epub ahead of print]
      A detailed understanding of the pathology of autoimmune diseases hinges on the identification of self-antigens and epitopes targeted by the immune system. While the characterization of autoantibodies is now well-established, facilitating both mechanistic insights and clinical biomarker applications, the identification of autoreactive T cell epitopes remains considerably more challenging. This complexity is amplified by the presence of autoreactive T cells in healthy individuals, necessitating highly sensitive and specific methods to allow for the detection of subtle differences between the autoreactive T cell population in healthy controls and in patients. Fortunately, T cell epitope discovery is a rapidly advancing field, with new methods continually emerging to improve sensitivity, throughput, and resolution. In this review, we will provide a structured overview of the key methods used to identify T cell epitopes, spanning both foundational techniques thathave been instrumental in the early discovery of self-epitopes involved in autoimmunity as well as recent high throughput approaches that offer enhanced precision and scalability. In the second part, we give an overview of the techniques used in the validation of the role of self-peptides in the autoimmune disorder. We conclude by discussing future directions in the field, emphasizing the critical role of T cell epitope discovery in driving the development of targeted, antigen-specific therapies for autoimmune disorders. This review aims to provide a practical and conceptual framework for T cell epitope discovery in autoimmune diseases, integrating established experimental approaches with emerging computational and high-throughput methodologies to guide informed method selection in contemporary research.
    Keywords:  Autoimmunity; Epitope discovery; T cell
    DOI:  https://doi.org/10.1016/j.ymeth.2026.02.004
  22. Immun Inflamm. 2025 ;1(1): 9
      T cells play an essential role in tumour prevention and control, however, avoidance or disruption of anti-tumour T cell responses frequently leads to tumour progression and malignant disease. Immunotherapy aims to address this breakdown in T cell-mediated anti-tumour immunity and restore T cell function to promote the elimination of cancerous cells. Although immunotherapy has led to drastic improvements in patient prognoses across a range of clinical setting, most patients still fail to exhibit a durable therapeutic response. In this review we discuss the role of T cells in controlling tumour progression, how T cell immunity is avoided or disrupted in the context of malignant disease, and the mechanisms by which soluble, cellular, or vaccine-based immunotherapies aim to restore anti-tumour T cell responses. This review does not aim to provide a comprehensive summary of approved immunotherapies, nor does it focus on the logistical challenges faced during the development or clinical application of immunotherapy. Instead, this review aims to highlight the mechanisms by which different therapeutic approaches address, or fail to address, specific aspects of the breakdown in T cell-mediated anti-tumour immunity. This review will also discuss exciting pre- and early-stage clinical developments that may improve the therapeutic efficacy and applicability of these treatments by more comprehensively addressing the challenges faced by T cells to improve patient prognoses.
    Graphical Abstract:
    Keywords:  Adoptive cell transfer; Cancer; Immune checkpoint blockade; Immunotherapy; T Cells; Vaccination
    DOI:  https://doi.org/10.1007/s44466-025-00007-z
  23. Arthritis Rheumatol. 2026 Feb 11.
       OBJECTIVE: Dual-target CAR-T cell therapy targeting BCMA and CD19 is an emerging and promising treatment for systemic lupus erythematosus (SLE). However, its effects on fertility and neonatal safety are largely unknown. This report describes the outcomes of two successful pregnancies and deliveries in a patient with SLE treated with BCMA/CD19 CAR-T cell therapy.
    METHODS: A 24-year-old woman with class IV lupus nephritis received BCMA/CD19 CAR-T cell therapy. The patient achieved sustained molecular remission of SLE and became pregnant spontaneously at 6-months and 21-months postinfusion. We monitored for CAR-T cell presence in maternal and neonatal samples and assessed the health of the infants.
    RESULTS: Lupus activity remained minimal without flares throughout both pregnancies. The patient had two term vaginal deliveries of healthy female infants. Serial digital polymerase chain reaction analysis of the patient's blood, breast milk, and placenta, as well as the infants' blood at birth and during follow-up, were all uniformly negative for CAR-T cell DNA. Both infants showed normal growth, neurodevelopment, and immune function at follow-up, with no evidence of CAR-T cell transmission. The patient's self-reported quality of life also improved significantly after the therapy.
    CONCLUSION: This case suggests that BCMA/CD19 CAR-T cell therapy may induce sustained remission (over 30 months) in SLE, preserve fertility, and result in healthy pregnancies and neonates. This finding highlights the need for evidence-based guidelines for patients considering pregnancy after CAR-T cell therapy.
    DOI:  https://doi.org/10.1002/art.70070
  24. Ann Pharm Fr. 2026 Feb 05. pii: S0003-4509(26)00007-6. [Epub ahead of print]
      The drug development pipeline remains extraordinarily complex, costly, and time-intensive, typically requiring 10-15 years and $2-3 billion per approved drug. This review presents a translational perspective on how artificial intelligence (AI) and machine learning (ML) are renovating pharmaceutical R&D across the entire value chain while maintaining rigorous safety and efficacy standards. In drug discovery, deep learning platforms enable virtual screening of billion-compounds, reducing target identification from years to months while improving hit rates by 30-50%. Preclinical development benefits from AI-powered toxicity prediction, potentially eliminating 40% of animal testing through accurate in silico models. Clinical trials are optimized through digital twin technology, reducing patient cohorts by 25-30% without compromising statistical power. Post-marketing surveillance is accelerated 100-fold through AI-driven real-world evidence analysis. Across the development lifecycle, AI delivers 30-60% time savings and 25-40% cost reductions while increasing success rates through enhanced predictive capabilities. Formulation development benefits from ML algorithms that optimize drug compositions and stability, reducing trial-and-error experimentation. However, challenges persist in data quality, algorithmic bias, and regulatory acceptance of AI-derived evidence. This review provides a balanced perspective on AI's transformative potential in drug discovery and various formulation developments, along with its limitations, offering a roadmap for successful implementation in pharmaceutical R&D.
    Keywords:  Artificial Intelligence; Drug Discovery; Formulation Development; Machine Learning; Regulatory Approvals
    DOI:  https://doi.org/10.1016/j.pharma.2026.01.007
  25. Front Cell Infect Microbiol. 2026 ;16 1721114
       Objective: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in hematological malignancies. However, it can also cause severe systemic toxicity, known as cytokine release syndrome (CRS). Therefore, the potential of CAR-T cells to cause toxicity in vivo should be evaluated in preclinical models prior to first-in-human trials. Although murine models exist for this purpose, they are typically complex xenograft systems available only to a limited number of laboratories. Therefore, development of an in vitro assay to assess CRS elicited by CAR-T cells is warranted.
    Methods: CAR-T cells, macrophages, or immature dendritic cells (iDCs), along with tumor target cells, were co-cultured under different conditions. The release of CRS-related cytokines, IFN-γ and IL-6, was measured to simulate cytokine release during CAR-T-induced CRS. Additionally, the cellular source of the key CRS cytokine IL-6 was investigated.
    Results: A co-culture system containing only CAR-T cells and tumor cells failed to recapitulate the key feature of CRS, specifically a significant elevation of IL-6. However, when CAR-T cells were co-cultured with antigen-presenting cells (macrophages or iDCs) and tumor cells, the core CRS cytokine IL-6 was significantly elevated in an in vitro cell culture model, indicating that this system effectively mimics cytokine release during CAR-T-induced CRS. Furthermore, macrophages and iDCs are the primary cellular sources of IL-6 during CRS, with macrophages playing a central role in the development of CRS. Additionally, a co-culture system involving CAR-T cells, tumor cells, and macrophages under these conditions can indicate the occurrence of clinically severe-grade CRS.
    Conclusion: Macrophages and iDCs play a critical role in the development of CAR-T therapy-induced CRS. The triple-cell co-culture system, comprising CAR-T cells, macrophages or iDCs, and tumor cells, provides a viable in vitro model for assessing CAR-T cell-induced CRS.
    Keywords:  CAR-T cells; CRS; cytokine release syndrome; in vitro assay; non-clinical safety evaluation
    DOI:  https://doi.org/10.3389/fcimb.2026.1721114
  26. Virulence. 2026 Dec;17(1): 2629132
      Staphylococcus aureus (S. aureus) bloodstream infections pose a significant clinical threat, exacerbated by increasing antibiotic resistance and high mortality. While the gut microbiota is recognized as a key modulator of systemic immunity, the mechanisms underlying its protective role against invasive bacterial infections remain incompletely understood. Here, we investigated how gut microbiota influences hepatic immune responses during early S. aureus bloodstream infection using animal models. Our findings demonstrate that the gut microbiota exerts a protective effect against systemic S. aureus infection. Specifically, commensal microbiota-derived signals prime hepatic γδ T cells for rapid interleukin-17A (IL-17A) production upon bacterial challenge. This microbiota-dependent IL-17A response subsequently promotes neutrophil recruitment to the liver, facilitating bacterial clearance and limiting systemic dissemination. Disruption of the gut microbiota impaired hepatic γδ T cell IL-17A production, reduced neutrophil mobilization, and compromised host resistance to infection. Notably, we found that colonization with the commensal Limosilactobacillus reuteri (L. reuteri) activates this hepatic γδT17-neutrophil axis, enhancing host defense against S. aureus as a mechanism involving indole metabolites. This study reveals a novel gut-liver axis whereby intestinal microbiota orchestrates hepatic γδ T cell function to establish an early immunological barrier against invasive bacterial pathogens, offering potential therapeutic avenues for enhancing host defense against life-threatening S. aureus infections.
    Keywords:  IL-17A; S. aureus; gut microbiota; neutrophils; systemic infection; γδ T cells
    DOI:  https://doi.org/10.1080/21505594.2026.2629132
  27. Biotechnol J. 2026 Feb;21(2): e70192
      Genetic stability is an important attribute of biotherapeutic production cells, and as such, regulatory agencies require that production cell lines exhibit genetic comparability throughout the entire manufacturing process when applying for a commercial license. Cell line selection typically occurs well before good manufacturing process (GMP) cell banks are available for genetic characterization, so it is important to develop tools for assessing genetic stability during early cell line development (CLD) that can reduce the risk of nominating a genetically unstable cell line for a commercial process. Herein, we describe the development of next-generation sequencing (NGS)-based methods and novel bioinformatic analyses to assess the genetic stability of cell lines. A targeted sequence capture (TSC) pipeline was applied to 82 clonally derived antibody-producing CHO cell lines to characterize genomic transgene sequence identity, genome integration sites, integrated vector sequence integrity, and copy number estimation for the development cell lines. The NGS data provided an early determination of genetic stability that was subsequently found comparable to traditional genetic characterization methods when GMP cell banks were available. These data demonstrate the utility of NGS to establish genetic stability early in the biotherapeutic manufacturing lifecycle and as a suitable method for genetic characterization.
    Keywords:  CHO cells; genetic characterization; next‐generation sequencing; targeted sequence capture
    DOI:  https://doi.org/10.1002/biot.70192
  28. Hum Immunol. 2026 Feb 10. pii: S0198-8859(26)00027-3. [Epub ahead of print]87(4): 111681
      Regulatory T cells (Tregs) represent a promising approach to induce donor-specific tolerance in cardiac transplantation, potentially reducing reliance on chronic immunosuppression. This review critically evaluates preclinical and clinical evidence. Preclinical studies demonstrate that adoptively transferred Tregs prolong cardiac allograft survival and prevent chronic allograft vasculopathy (CAV) in murine models through multiple suppressive mechanisms. Phase I/II trials in kidney and liver transplantation have already confirmed safety and feasibility of polyclonal Treg cell therapy, with evidence of immunosuppression reduction in selected patients. However, no cardiac-specific trials have been completed in adults, and critical translational barriers persist including limited in vivo persistence, phenotypic instability under inflammatory conditions, manufacturing complexity and incompatibility with deceased donor timelines. Emerging approaches show promise: CAR-engineered Tregs targeting HLA-A2 demonstrate enhanced specificity and establish infectious tolerance in preclinical cardiac transplant models, with preliminary data from the first-in-human kidney transplant data suggesting safety and efficacy. Thymus-derived Tregs offer advantages for pediatric recipients, with the first treated cardiac transplant patient showing preserved Treg homeostasis. This review identifies key research priorities necessary to translate Treg therapy into clinical cardiac transplantation practice.
    Keywords:  Cardiac Allograft Vasculopathy; Cell therapy; Immune Tolerance; Regulatory T Cells; Transplantation
    DOI:  https://doi.org/10.1016/j.humimm.2026.111681
  29. PLOS Glob Public Health. 2026 ;6(2): e0005914
      Healthcare systems worldwide face mounting pressures from aging populations, costly medical technologies, and rising healthcare expenditures. Health Technology Assessment (HTA) has emerged as a critical tool for improving efficiency and supporting evidence-informed resource allocation through systematic evaluation. In Brazil, HTA plays a central role in advancing Universal Health Coverage (UHC), particularly through the National Committee for Health Technology Incorporation (Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde - CONITEC). As HTA continues to evolve in Brazil, there is an increasing need for health policy and systems research to better understand its structure, challenges, and opportunities. This study aimed to comprehensively analyze the key pillars of Brazil's national HTA system, identify existing barriers, and propose strategies to strengthen HTA processes. A mixed-methods approach was employed between 2021 and 2023, targeting HTA-related organizations and experts across multiple health sectors. Data were collected through thirteen electronic institutional surveys assessing technical aspects of HTA and nine virtual in-depth interviews exploring HTA from a policy perspective. Findings indicate a strong presence of public-sector and academic institutions within Brazil's HTA landscape, alongside broad recognition of HTA's value and CONITEC's central role in coordinating evidence generation and appraisal. However, challenges such as potential conflicts of interest and reliance on exclusive government funding were identified, underscoring the need for more diversified and sustainable financing mechanisms. The system benefits from a multidisciplinary workforce and active community participation, and HTA evidence is widely used in policymaking, particularly in evaluating clinical effectiveness, costs, and economic value. Despite these strengths, limitations persist, including insufficient institutional capacity, resource constraints, and political support. Participants emphasized the need to strengthen HTA skills, competencies, and coordination to improve the effectiveness and impact of HTA processes. This study contributes to the limited literature on Brazil's HTA system and provides evidence to inform future research and policy efforts aimed at strengthening HTA integration in support of UHC.
    DOI:  https://doi.org/10.1371/journal.pgph.0005914
  30. Biochem Mol Biol Educ. 2026 Feb 14.
      This review critically examines the integration of Digital Information and Communication Technologies (TDICs) in biochemistry education over the past decade, highlighting both the benefits and challenges from a critical theoretical perspective. A systematic review was conducted to identify relevant literature, followed by thematic analysis and a detailed synthesis of the findings. Grounded in Feenberg's critical theory of technology and Selwyn's scholarship on education and digital technology, this review examines the implications of virtual laboratories, augmented reality, gamification, and online platforms in biochemistry education, as well as their implications related to the pandemic. We observed that digital technologies can enhance certain aspects of student engagement and learning outcomes; however, they can also hinder equitable access and hands-on laboratory skills. This review also highlights the key elements of critical reflection on the socio-political and ethical implications of digital technologies in biochemistry education, with a particular focus on pandemic-era concerns, including data privacy, algorithmic bias, and the commercialization of teaching practices. Future research should focus on these dimensions to ensure that technological advancements do not perpetuate or amplify educational inequities.
    Keywords:  COVID‐19; augmented reality; biochemistry education; critical perspective on the use of DICTs; gamification; integration of digital information and communication technologies (DICT); platforms; virtual laboratory
    DOI:  https://doi.org/10.1002/bmb.70038
  31. JMIR Cancer. 2026 Feb 11. 12 e82448
       Background: The number of cancer survivors is steadily increasing worldwide, leading to an increased demand for long-term follow-up and supportive care. Many survivors face ongoing physical and psychosocial issues that highlight the need for innovative management approaches. Mobile health apps offer potential benefits by facilitating patient-led follow-up, self-management, and more efficient use of health care resources. Although the market for cancer-related mobile apps has grown rapidly, their sustainability and scientific basis remain unclear. In the European Union, the Medical Device Regulation (MDR), in effect since May 2021, introduced stricter criteria for classifying medical devices, including certain software apps. While aiming to improve patient safety, the MDR could pose challenges for small companies and academic developers, potentially limiting the availability of such apps. No scoping review has delineated changes in active apps before and after implementation of the legislation regulating medical devices.
    Objective: This scoping review aimed to evaluate the current availability and longevity of English-language mobile apps supporting cancer recovery, with a specific focus on changes before and after the implementation of the European Union MDR, and to assess the extent to which these apps are supported by clinical evidence.
    Methods: Searches were conducted in mobile app stores (Apple's App Store and Google Play) and literature databases (MEDLINE, Embase, Cochrane Library, and Web of Science), using predefined terms. Mobile apps targeting cancer recovery and published articles on their effectiveness were included. Two reviewers independently extracted data. A descriptive analysis was conducted to report trends in mobile device app availability and updates over time.
    Results: A total of 151 mobile apps were identified in 2018. However, by 2024, only 45 of 151 (30%) were still available. Among these, 25 of 151 (17%) were updated within the past 2 years. During the search in December 2024, 1 new mobile app supported by scientific evidence was discovered. This mobile app was developed to assist cancer survivors in managing insomnia through cognitive behavioral therapy. Rapid turnover and a potential lack of sustainability in the mobile health app market for cancer survivors were evident, with most mobile apps identified in 2018 no longer available by 2024.
    Conclusions: This review revealed a limited number of publicly available mobile apps that support cancer recovery. The longevity of existing mobile apps is limited, potentially because of regulatory and financial barriers. Prioritizing rigorous effectiveness trials, addressing implementation barriers, and developing sustainable business models are essential to ensure the long-term availability and success of mobile health apps in cancer survivorship care.
    Keywords:  cancer; cancer survivorship; mobile health; neoplasm; symptoms
    DOI:  https://doi.org/10.2196/82448
  32. Mutagenesis. 2026 Feb 09. pii: geag003. [Epub ahead of print]
      Animal models have been key for disease mechanism research for years, but ethical concerns partly fuelled by the realisation that not all diseases can be recapitulated in animal systems have led to regulatory changes that are driving a shift towards animal-free alternatives. As regulations continue to evolve, the transition to animal-free models is becoming increasingly crucial for laboratories aiming to comply with new standards without compromising on scientific progress. The past decade has seen a boost in the development of animal-free three-dimensional models including explants, co-cultures, spheroids, organoids, and organ-on-chip systems, creating a varied landscape that has significantly transformed disease research. These models incorporate advancements in stem cell technology, bioengineering, and microfluidics to provide more physiologically relevant systems that bridge the gap between traditional two-dimensional cell culture and in-vivo studies. Whilst traditional two-dimensional cultures offer a cost-effective method with replicable results, they fail to accurately represent the natural structure of tissues and cell-cell interactions. By contrast, animal-free culture systems provide a more appropriate representation of human physiology and tissue architecture with relevance to in-vivo conditions. Therefore, these models enable more translatable research outcomes and have the potential to provide data for the reduction of the high failure rates currently marring clinical trials. This review explores the evolution, advantages, and applications of animal-free models in advancing human disease research and refining preclinical studies with an emphasis on cancer research.
    Keywords:  animal-free models; disease mechanisms; drug discovery; organoids; patient-derived explants
    DOI:  https://doi.org/10.1093/mutage/geag003
  33. Semin Immunol. 2026 Feb 10. pii: S1044-5323(26)00003-5. [Epub ahead of print]81 102016
      Autoimmune diseases of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), are characterized by chronic inflammation driven by autoreactive immune responses against CNS antigens. Successes in the development of efficacious immunotherapies are hampered by the risks of broad immunosuppression and the consequences of compromising physiological immune functions. Antigen-specific immune tolerance offers a promising alternative by selectively silencing pathogenic immune responses while preserving global immune competence. Advances in understanding of pathophysiology and target antigens in multiple sclerosis, neuromyleitis optica spectrum disroders (NMOSD) myelin oligondendrocyte protein (MOG) antibody associated disease (MOGAD) have enabled the development of antigen-based tolerization strategies. These approaches primarily act through restoration of peripheral tolerance via modulation of autoreactive T and B cell responses. Clinical trials in MS and NMOSD have provided critical insights into key challenges of translation and clinical development, including optimal antigen selection, route of administration, patient stratification and trial design constraints. Future progress in MS, NMO and MOGAD will also depend on precise characterization of immunodominant epitopes and the development of standardized biomarkers of tolerance induction and their integration in novel trial designs. Successful induction of durable, antigen-specific immune tolerance would represent a paradigm shift in treating CNS autoimmunity, enabling disease-specific, safe, and sustained remission without generalized immunosuppression.
    Keywords:  Autoimmune disease; Central nervous system; Immune tolerance; Immunotherapy
    DOI:  https://doi.org/10.1016/j.smim.2026.102016
  34. Transl Pediatr. 2026 Jan 31. 15(1): 5
       Background: Chimeric antigen receptor T (CAR-T) cells have achieved breakthrough results in the treatment of refractory/relapsed leukemia in children. With the continuous development of research and increasing clinical application, infection events after CAR-T cell therapy have gradually attracted the attention of researchers. Lower respiratory tract infection (LRTI) events accounted for 19.2% of the total number of infection events and resulted in patient death. This study aims to investigate the risk factors of LRTI in children with leukemia who received CAR-T cell therapy and construct a risk predictive model.
    Methods: The clinical data of children with leukemia receiving CAR-T cell therapy in a tertiary A children's hospital in Shanghai from November 2023 to December 2024 were retrospectively collected, and the independent risk factors for LRTI were analyzed, and a risk predictive model was constructed. The Hosmer-Lemeshow test and the area under the receiver operating characteristic (ROC) curve were used to evaluate the fitting degree and discrimination of the predictive model, and a nomogram was constructed to visualize the model.
    Results: A total of 265 cases were included in this study, and the incidence of LRTI within 0-30 days after CAR-T cell therapy was 14.7%. The risk factors for developing LRTI were platelet count (PLT) <50×109/L (X1), minimal residual disease (MRD) >20% (X2), dosage of dexamethasone greater than 10 mg (X3), and allogeneic CAR-T (X4), and the regression equation was: occurrence y (incidence of LRTI) = 1.027 × X1 + 1.079 × X2 + 1.187 × X3 + 1.096 × X4. Hosmer-Lemeshow test showed that χ2 was 2.674 (P=0.95). The area under the ROC curve was 0.781 (P<0.001), the maximum Youden index was 0.468, the cut-off value was 0.139, the sensitivity was 76.9%, and the specificity was 69.9%.
    Conclusions: In this study, a risk predictive model for LRTI in children with leukemia within 0-30 days after CAR-T cell therapy was constructed. The predictive factors were PLT <50×109/L, MRD >20%, dexamethasone use greater than 10 mg, and allogeneic CAR-T.
    Keywords:  Chimeric antigen receptor T (CAR-T); leukemia; lower respiratory tract infection (LRTI); predictive model
    DOI:  https://doi.org/10.21037/tp-2025-503
  35. Environ Res. 2026 Feb 08. pii: S0013-9351(26)00253-7. [Epub ahead of print] 123925
      In the context of the global strategy of sustainable development and carbon neutrality, green catalytic technology, as the core of achieving efficient and clean chemical conversion, has a complex and uncertain path from laboratory innovation to large-scale commercial application. The traditional R&D and commercialization models are often limited by bottlenecks such as high trial and error costs, long cycles, and difficulties in coupling and analyzing multi-scale factors. This review is based on the perspective of technology lifecycle management and systematically explores how data-driven paradigms, especially machine learning methods, can profoundly reshape the full chain management logic of green catalytic technology from conceptual design, process development, engineering scaling up to market deployment. The article first analyzes the core challenges and data requirements of each stage of commercialization of green catalytic technology (basic research, concept validation, process optimization, pilot scale, commercial operation), pointing out that it is essentially a complex system optimization problem with multiple objectives and constraints. Furthermore, this article provides an in-depth overview of the cutting-edge applications and typical cases of machine learning in key areas such as intelligent design and screening of catalytic materials (such as high-throughput virtual screening, structure-activity relationship modeling), reaction mechanism analysis and kinetic simulation, intelligent optimization of reactor design and process conditions, as well as full lifecycle environmental impact and economic technology analysis. The advantages and limitations of different paradigms such as supervised learning, unsupervised learning, reinforcement learning, and generative models in solving specific problems were analyzed in detail. Finally, this article critically summarizes the common challenges faced by the current data-driven path, including the scarcity of high-quality datasets, interpretability and physical consistency of models, and integration difficulties in cross scale modeling. It also looks forward to future research directions, such as physical information machine learning that integrates domain knowledge, the construction of standardized data platforms, and the development of intelligent decision support systems for human-machine collaboration. This review aims to provide a systematic framework and forward-looking guidance for interdisciplinary research in the fields of catalytic science, chemical engineering, and data science, accelerating the commercialization of green catalytic technology in a more efficient and predictable manner, and serving the construction of green manufacturing systems.
    Keywords:  Data driven; green catalysis; lifecycle management; machine learning; technology commercialization
    DOI:  https://doi.org/10.1016/j.envres.2026.123925
  36. Pharmacoepidemiol Drug Saf. 2026 Feb;35(2): e70296
       PURPOSE: An increasing number of studies based on secondary data use, including registry-based studies, have been initiated to address post-authorization regulatory commitments. We map differences across tools used in data quality (DQ) assessments, including those embedded in fitness-for-purpose (FFP) assessments, and describe their strengths and limitations for use in DQ assessments of registries considered for use in post-approval safety studies (PASS). We focus on the use case where marketing authorization holders (MAHs) cannot directly analyze patient-level data. Furthermore, we propose complementary measures to improve DQ assessment, including a set of data quality indicators (DQIs).
    METHODS: We analyzed the extent to which the selected tools used in registry assessments address DQ dimensions and metrics defined in the European Medicines Agency-DQ Framework (EMA-DQF). We specifically considered the use case where DQ assessment was purely based on registry documentation and qualitative due to data access restrictions.
    RESULTS: None of the tools covered all DQ dimensions and metrics; they had limited utility for evaluating extensiveness (i.e., completeness and coverage), semantic coherence, and reliability (i.e., accuracy and plausibility). Furthermore, some supporting document requirements were more useful than others. For example, the data dictionary is useful for evaluating precision and structural coherence. In contrast, publications have limited utility in DQ assessment.
    CONCLUSIONS: We propose a set of consistent definitions of information requirements and quantitative DQIs that complement existing tools that can be used for evaluating DQ throughout the registry-based PASS lifecycle. If DQIs cannot be evaluated during the preparation of the PASS protocol, uncertainties and their potential impact on the study results need to be acknowledged in the relevant study documents. Additionally, scenario mapping for the removal or replacement of registries with insufficient DQ after PASS initiation is needed.
    Keywords:  data quality indicators; patient registries; post‐authorization safety studies
    DOI:  https://doi.org/10.1002/pds.70296
  37. J Healthc Inform Res. 2026 Mar;10(1): 179-208
      The reuse of clinical health data holds immense promise for advancing medical research, yet remains constrained by complex legal, technical, and organisational barriers. This article examines these challenges through the case study of TumorScope, a Belgian interdisciplinary initiative developing a secure, multimodal data environment for glioblastoma research. Drawing on five years of practical experience integrating imaging, genetic, tissue-based, and clinical datasets, the study identifies key legal, ethical, technical, and operational obstacles to effective data access, linkage, and reuse. Technical issues included fragmented data flows, pseudonymisation complexities, and limited interoperability, while legal and ethical barriers arose from strict interpretations of the General Data Protection Regulation, medical secrecy obligations, and intellectual property constraints. These were compounded by operational challenges such as unclear governance structures, resource limitations, and the limited capacity of Medical Research Ethics Committees to assess data-driven research. The analysis further considers the European Health Data Space Regulation (EHDS) as a potential enabler of responsible secondary data use, while noting uncertainties in its national implementation. Overall, the study demonstrates that meaningful health data reuse requires more than regulatory compliance, it depends on robust governance frameworks, institutional coordination, and sustained investment in infrastructure and expertise. The findings contribute to ongoing debates in healthcare informatics on how to translate the vision of the EHDS into practical, ethically grounded data reuse for patient benefit.
    Keywords:  Data governance; European Health Data Space (EHDS); Interdisciplinary data sharing; Multimodal data integration; National implementation; Secondary use of health data; Secure processing environment
    DOI:  https://doi.org/10.1007/s41666-025-00220-w
  38. Stud Health Technol Inform. 2026 Feb 12. 334 132-134
      Canada's healthcare system is moving toward digital transformation, but progress is slowed by persistent silos between clinical research, frontline practice, entrepreneurship, and policy. Global strategies emphasize that governance, equity, and workforce capacity are just as important as technology. In Canada, national reports highlight the need for integrated data sharing across regions and sectors. This paper presents an early case study of The Human Puzzle, a grassroots initiative launched in 2025 by an undergraduate student in applied mathematics. What began as a small experiment convening students, researchers, clinicians, and entrepreneurs revealed both the strong demand for cross-disciplinary spaces and the gaps in existing training and career pathways.. Two inaugural events, Biology Meets AI (125 participants) and Sensors, Structures, and Systems (115 participants with a 60-person waitlist), confirmed this need. The conversations sparked during and after these events shaped the initiative's next stage: mentorship pipelines, applied skills workshops, hackathons, and incubation supports. These grassroots pilots are not a substitute for system-level reform, but they generate early evidence about how bottom-up energy can complement national efforts. By testing collaborative models at a small scale, The Human Puzzle contributes to the broader movement from silos to synergy in digital health.
    Keywords:  Community-Driven Innovation; Digital Health; Interdisciplinary Innovation; Policy & Governance; Workforce Development
    DOI:  https://doi.org/10.3233/SHTI260035
  39. J Nanobiotechnology. 2026 Feb 09.
      The advancement of nanotechnology has revolutionized reproductive healthcare worldwide. It has enabled the treatment of various conditions, such as infertility, endometriosis, ectopic pregnancies, erectile dysfunction, sexually transmitted infections (STIs), and reproductive tissue cancers. Nanotechnology offers improved imaging, personalized drug administration, and early diagnosis, leading to more accurate treatment outcomes. It can enhance fertility preservation, improve individualized therapy, and improve diagnostic methods. Additionally, nanotechnology-powered drug delivery systems increase effectiveness while reducing side effects. Clinical trials utilizing nanoparticles for cellular treatments, targeted drug delivery, early infection detection, reproductive system malignancies and precise medication delivery are currently underway. Nanotechnology has opened new possibilities in areas such as disease detection, drug administration, diagnostic imaging, and cancer treatment. This review aims to provide an overview of the different types, characteristics, and synthesis methods of nanocarriers designed for medication delivery in the context of reproductive disorders and diseases. It seeks to enhance the understanding of the current state of the art and explore potential future advancements in this field.
    Keywords:  Biosensor; Nanotechnology; Reproductive health; Targeted drug delivery
    DOI:  https://doi.org/10.1186/s12951-025-03898-7
  40. Value Health. 2026 Feb 10. pii: S1098-3015(26)00049-5. [Epub ahead of print]
      Health technology assessment (HTA) must increasingly incorporate environmental sustainability (ES) to ensure digital health technologies (DHTs) deliver true value for both population and planetary health. Existing HTA frameworks inadequately capture the upstream and downstream environmental implications of DHTs, overlooking critical factors such as energy consumption, data storage, water usage and electronic waste. Using a few examples on telehealth platforms, electronic health records and artificial intelligence (AI) driven diagnostic tools, we illustrate how these technologies can reduce carbon emissions and other pollutants by limiting patient travel and optimizing resource use. We review current HTA frameworks, identify ongoing initiatives, and highlight gaps and challenges in integrating ES into value assessment. Traditional HTA models provide limited guidance for incorporating broad environmental factors, risking underestimation of DHTs' environmental impacts and potentially undermining health systems' net-zero commitments by 2050. To address these issues, in this commentary, we propose for targeted investment in frameworks, streamlined environmental data collection, and stronger cross-sector collaboration. Systemic inclusion of ES can reduce inequalities, support ethical supply chains and incentivize developers to design lower-impact technologies, positioning HTA as a driver of sustainable digital health innovation. By embedding environmental metrics, health systems can better balance clinical benefits, economic efficiency and ecological responsibility, thereby advancing both human and planetary health.
    Keywords:  Digital Health; climate change; health economics; health technology assessment; sustainability
    DOI:  https://doi.org/10.1016/j.jval.2026.01.019
  41. J Clin Oncol. 2026 Feb 11. JCO2502087
      Clinical trials and real-world evidence have established the benefit of chimeric antigen receptor (CAR) T-cell therapy to reduce progression of hematologic malignancies and, in some settings, increase overall survival. However, recent studies have highlighted that patients in long-term remission remain at risk of morbidity and nonrelapse mortality, primarily because of infections and subsequent myeloid malignancies. In addition, these patients may also be survivors of chemotherapy, radiation, and/or stem-cell transplant, with broad survivorship needs. Here, we provide a roadmap for the care of patients in long-term remission after CAR-T-cell therapies and discuss avenues for future research.
    DOI:  https://doi.org/10.1200/JCO-25-02087
  42. MAbs. 2026 Dec;18(1): 2623330
      The development of computational models addressing therapeutic antibodies faces significant challenges. Particularly, the prediction of binding affinity across a diverse set of measurements, due to the scarcity of data. A critical data element is the set of antibody-antigen interaction pairs associated with sequences. To address this issue, we developed the Antigen Specific Antibody Database (ASD, https://naturalantibody.com/agab/), a database aggregating antibody-antigen interaction data from multiple studies with standardized formatting and annotations. Our dataset compilation strategy resulted in data from 15 distinct sources, resulting in 1,097,946 unique antibody-antigen interactions (with 9575 unique antigens). The ASD captures diverse affinity measures and qualitative binding assessment, along with metadata including UniProt and PDB identifiers, target protein names, confidence levels, and experimental conditions such as type of measured affinity, source organism, and germline genes. Through this integration drive, we make available an ample resource of interaction data gathered from the public domain to act as a foundation for model development and further data generation.
    Keywords:  Antibody design; binding affinity; bioinformatics; computational immunology; databases; drug discovery
    DOI:  https://doi.org/10.1080/19420862.2026.2623330
  43. Cells. 2026 Jan 23. pii: 212. [Epub ahead of print]15(3):
      Gene and cell therapies have become core components of regenerative medicine, moving from proof-of-concept studies toward clinically actionable strategies for repairing or replacing damaged tissues [...].
    DOI:  https://doi.org/10.3390/cells15030212