bims-carter Biomed News
on CAR-T Therapies
Issue of 2026–01–18
forty-one papers selected by
Luca Bolliger, lxBio



  1. Handb Clin Neurol. 2026 ;pii: B978-0-323-90887-0.00012-2. [Epub ahead of print]214 439-451
      Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, and its application in neuroimmunologic autoimmune diseases is now emerging as a promising therapeutic avenue. Neuroimmunologic diseases such as multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorder, and stiff-person syndrome have shown varying degrees of response to traditional immunomodulatory therapies, but a significant proportion of patients remain refractory to treatment. In recent studies, anti-CD19 CAR T cells have shown encouraging results in targeting B cells, a key driver of autoimmune pathogenesis. CAR T-cells can penetrate the central nervous system and overcome the limitations of conventional B-cell depleting therapies such as rituximab, particularly in accessing ectopic lymphoid follicles that maintain compartmentalized inflammation. In early clinical cases, CAR T-cell treatment has resulted in marked clinical improvements, including significant reductions in symptoms and durable disease remission, with manageable side-effects. In addition, advances in allogeneic CAR T cell constructs and chimeric autoantibody receptor T cells offer additional avenues for precision-targeted therapies. These developments underscore the potential of CAR T cells to reshape the treatment landscape for refractory neuroimmunologic autoimmune diseases and warrant further controlled trials and regulatory exploration.
    Keywords:  Autoimmune disorders; CAR T cells; Cell therapy; Immunologic reset; Neuroimmunology
    DOI:  https://doi.org/10.1016/B978-0-323-90887-0.00012-2
  2. Indian J Dermatol Venereol Leprol. 2026 Jan-Feb;92(1):pii: 10.25259/IJDVL_1877_2025. [Epub ahead of print]92(1): 52-59
      Chimeric antigen receptor (CAR) T-cells are autologous T-cells genetically engineered to express an antigen receptor that can recognise and kill cells expressing that target antigen. Originally developed for refractory or relapsed B-cell and plasma cell malignancies, CAR T-cell therapy is now being explored as a promising treatment for B-cell-mediated autoimmune diseases. CAR-T cells produce 'deep' B-cell depletion and cause 'resetting' of the immune system, thereby achieving long-lasting remissions and potentially even 'cure', addressing some major limitations of current immunosuppressive and biological therapies. This narrative review discusses the current status of CAR T-cell therapy, along with its potential future applications, for dermatological disorders.
    Keywords:  Adoptive T cell transfer; CAAR-T cell; CAR-T cell; autoimmune disease; chimeric antigenic receptor T cell therapy
    DOI:  https://doi.org/10.25259/IJDVL_1877_2025
  3. Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 Nov 20. 56(6): 1459-1466
      Regulatory T cells (Tregs) are the most important population of immune cells in maintaining peripheral immune tolerance in the body. Targeting Tregs to rebuild peripheral immune tolerance has shown broad potential for application in the treatment of various inflammatory diseases, such as autoimmune diseases, allergic disorders, graft-versus-host disease, and organ transplant rejection. However, substantial challenges remain in translating Treg-based therapies into clinical practice. In this review, we first summarize the discovery of Tregs and the principal mechanisms through which Tregs inhibit immune responses. Then, the research progress in polyclonal Treg-based therapy, antigen-specific Treg-based therapy, and low-dose interleukin-2 (IL-2) therapy and the implementation status of clinical trials of Treg therapies were comprehensively summarized. Finally, four issues, including maintaining the stability of Tregs, preparing autoantigen-specific Tregs, such as chimeric antigen receptor (CAR)-Tregs and T-cell receptor (TCR)-Tregs, reshaping the inflammatory microenvironment of diseases, and minimizing the potential adverse effects of Treg therapies, were highlighted as the bottleneck problems in the clinical translation of Treg therapies and priority directions for future research.
    Keywords:  Autoimmune diseases; Foxp3; Graft-versus-host disease; Immunotherapy; Low-dose interleukin-2 therapy; Regulatory T cell therapy; Review
    DOI:  https://doi.org/10.12182/20251160301
  4. Immune Netw. 2025 Dec;25(6): e43
      Chimeric Ag receptor (CAR)-T cell therapy has demonstrated success primarily in B-cell malignancies, but efficacy in solid tumors remains limited by Ag heterogeneity, immunosuppressive tumor microenvironments, and restricted infiltration. Cytokine engineering has emerged as a promising strategy to overcome these barriers. Fourth-generation CAR-T cells, known as T cells redirected for universal cytokine-mediated killing, demonstrated the feasibility of localized immune modulation through activation-induced IL-12 release, and this concept has been extended to various cytokines. Receptor engineering strategies, including switch/inverted and orthogonal designs, restrict cytokine signaling to CAR-T cells, thereby enhancing both specificity and safety. Beyond CAR-T engineering, external cell-based 'cytokine factories' and immune-cytokines further underscore the versatility of localized cytokine delivery strategies. In addition, fifth-generation CAR-T cells, incorporating approaches that enhance or mimic cytokine-mediated JAK-STAT signaling pathways, highlight a new direction toward programmable intracellular signaling. These strategies remain in the early stages of clinical application due to substantial limitations related to safety and clinical translation, including risks of uncontrolled cytokine activation and complexities in manufacturing. Nevertheless, they offer significant potential to improve therapeutic outcomes not only in hematologic malignancies but also across a broad range of solid tumors.
    Keywords:  CAR T-cell therapy; Cancer; Cytokine; Immunotherapy
    DOI:  https://doi.org/10.4110/in.2025.25.e43
  5. Ann Hematol. 2026 Jan 15. 105(1): 20
      Acute myeloid leukemia (AML) is a high-risk hematologic malignancy with poor long-term survival and frequent relapse, sustained by leukemic stem cells, antigenic heterogeneity, and an immunosuppressive bone marrow niche. Although chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in B-cell malignancies, its application in AML is restricted by on-target myelotoxicity from antigen overlap with normal progenitors, heterogeneous and dynamic antigen expression, rapid T-cell exhaustion in suppressive microenvironments, limited manufacturing windows with compromised T-cell quality, and uncertainty in optimal infusion timing. To address these barriers, logic-gated and adapter CARs are engineered to broaden antigen recognition while limiting toxicity; nanobody-based CARs provide stable, low-immunogenic binding; gene-edited hematopoietic stem and progenitor cells permit AML clearance without prolonged marrow suppression; and metabolic or epigenetic modulation is employed to sustain T-cell function in hostile niches. Allogeneic CAR-T platforms offer a potential means to overcome manufacturing constraints and improve treatment accessibility. In selected settings, sequential CAR-T therapy and hematopoietic stem cell transplantation consolidate remission and restore hematopoiesis. This review integrates current and emerging AML antigen targets with engineering innovations into a structured translational framework, directly addressing the biological, manufacturing, and application barriers unique to AML, and outlining strategies with the potential to advance CAR-T therapy from experimental studies to durable clinical benefit.
    Keywords:  Acute myeloid leukemia; Adapter CAR-T cells; Allogeneic CAR-T cells; CAR-T therapy; Gene editing; Logic-gated CAR-T cells
    DOI:  https://doi.org/10.1007/s00277-026-06742-6
  6. J Immunother Cancer. 2026 Jan 16. pii: e013325. [Epub ahead of print]14(1):
      B cell acute lymphoblastic leukemia (B-ALL) is the most common cancer of childhood. Outcomes for B-ALL have steadily improved over the last five decades, most recently due to impressive activity of chimeric antigen receptor modified T (CAR-T) cells and bispecific antibodies targeting CD19. In contrast, progress against other pediatric cancers has largely stalled. Significant academic effort is underway to expand the reach of CAR T cell therapy in pediatric cancer beyond B-ALL to other hematologic malignancies, solid cancers and brain tumors. Promising clinical activity using CAR-modified T cells has already been demonstrated in neuroblastoma and diffuse midline glioma by targeting the GD2 ganglioside, in pediatric sarcomas by targeting Her2, in Hodgkin's disease by targeting CD30, in T cell lymphoblastic leukemia by targeting CD5 or CD7, and in CAR19 refractory B-ALL by targeting CD22. Comprehensive surfaceome profiling of pediatric tumors is revealing additional novel candidate CAR targets expressed on pediatric cancers, including oncofetal cell surface antigens such as GPC2 and GPC3, which are expressed broadly on pediatric solid and brain tumors, and major histocompatibility complex bound peptides from oncofetal intracellular proteins such as PHOX2B Next-generation CAR T cell therapeutics that incorporate suicide domains, regulatory circuits, logic gating and potency enhancements as well as combination immunotherapies are expected to further augment efficacy while maintaining safety. Current trials are administering CAR T cells in patients with refractory disease, but future studies are warranted to determine whether adjuvant use of CAR T cells could deliver cures with lower intensity standard therapy regimens and thereby reduce long-term toxicities in pediatric cancer survivors. Despite this scientific and clinical progress, the high cost of developing CAR T cells through the traditional biopharma pathway is limiting late-stage clinical development, necessitating the creation of new business models to commercialize CAR T cells for these small markets. CAR T cells hold great promise for improving outcomes for pediatric patients with cancer, but substantial additional research and clinical development is needed if this promise is to be realized for children afflicted with cancer.
    Keywords:  Chimeric antigen receptor - CAR; Hematologic Malignancies; Survivorship
    DOI:  https://doi.org/10.1136/jitc-2025-013325
  7. Trends Mol Med. 2026 Jan 15. pii: S1471-4914(25)00293-X. [Epub ahead of print]
      Single cell RNA sequencing (scRNA-seq) has revolutionized the field of biology and become the most powerful tool for evaluating transcriptional profiles of a biological sample. Given its power, it is widely utilized across multiple disciplines, including chimeric antigen receptor (CAR)-T cell therapy. In this review, we provide a comprehensive summary of published studies that have used scRNA-seq to analyze clinical CAR-T cells, focusing on T cell exhaustion, cytotoxicity, memory, expansion, clonal diversity, and cytokines. We also highlight findings on activation, CD4+/CD8+ ratios, proliferation, regulatory T cells (Tregs) and metabolism, and their relevance to patient response across diseases. Finally, we discuss the limitations and future directions of scRNA-seq in CAR-T cell research, providing key insights for clinicians and researchers.
    Keywords:  CAR T cell; T cell fitness; patient sample; scRNA-seq
    DOI:  https://doi.org/10.1016/j.molmed.2025.12.006
  8. Hepatol Commun. 2026 Feb 01. pii: e0888. [Epub ahead of print]10(2):
       BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has shown promise in treating hematological malignancies. However, the complex tumor microenvironment of cholangiocarcinoma (CCA) poses significant challenges, particularly due to the lack of clinically validated targets and the presence of fibrosis, which hinders T cell infiltration into tumor sites. Mesothelin (MSLN) is highly expressed in CCA. In this study, we aimed to develop CAR T therapy based on a panel of humanized rabbit monoclonal antibodies targeting various epitopes of MSLN, ranging from the N- to the C-terminus, for CCA.
    METHODS: MSLN expression was assessed in CCA tissue samples obtained from Thai patients. CAR T cells were generated using various single-chain variable fragment (scFv) constructs, engineered in either VH-linker-VL or VL-linker-VH orientation, targeting non-overlapping epitopes of membrane-bound MSLN: hYP218 (proximal region), hYP223 and hYP3 (middle region), and hYP158 (distal region). The cytotoxicity of MSLN-specific CAR T cells was evaluated in 3 preclinical CCA mouse models: Mz-ChA-1, KMCH, and KMBC.
    RESULTS: MSLN was strongly expressed in 79% of the CCA specimens. Among the CAR constructs, hYP218-based CAR T cells-with the VL-linker-VH orientation and CD28-derived hinge and transmembrane domains (CD28HTM)-completely eradicated CCA tumors in all 3 CCA xenograft mouse models (Mz-ChA-1, KMCH, and KMBC). Furthermore, hYP218 VLVH CD28HTM CAR T cells showed strong persistence in mice, with low PD-1 expression (a marker of T cell exhaustion) and minimal adverse effects.
    CONCLUSIONS: Our findings suggest that MSLN is a promising target for CAR T cell therapy in CCA. CAR T cells engineered with hYP218 VLVH CD28HTM, which targets the membrane-proximal epitope of MSLN, may represent a novel therapeutic strategy for the clinical treatment of CCA.
    Keywords:  bioluminescence tumor imaging; cell immunotherapy; epitope mapping; hYP218 antibody; humanized rabbit monoclonal antibody; liver cancer; xenograft mouse model
    DOI:  https://doi.org/10.1097/HC9.0000000000000888
  9. J Immunother Cancer. 2026 Jan 12. pii: e013396. [Epub ahead of print]14(1):
      Sarcomas are rare malignancies of mesenchymal origin, characterized by significant biological and clinical heterogeneity. Many subtypes demonstrate limited sensitivity to standard systemic treatments, including immune checkpoint inhibitors. Cell therapy has emerged as a promising strategy, with the potential of durable clinical responses seen with genetically-engineered T-cell receptor T-cell therapies (TCR-T) such as those targeting the cancer-testis antigen MAGE-A4 in synovial sarcoma, leading to the US Food and Drug Administration approval of afamitresgene autoleucel in 2024. This constituted only the second approval of a cell therapy in a solid tumor following lifileucel in melanoma and demonstrated the potential of cell therapies in sarcomas. This review provides the current landscape and growing potential of cell therapies in sarcomas, including TCR-T, chimeric antigen receptor-T cells, tumor-infiltrating lymphocytes, natural killer (NK) cells, and mesenchymal stromal cells. However, the broader application of these therapies is hindered by the lack of targetable sarcoma-restricted immunogenic epitopes, spatiotemporal intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment that impedes effector-cell trafficking, expansion and persistence. While cell therapies hold promise for integration into precision medicine approaches for sarcomas, their successful implementation will require careful evaluation of clinical feasibility, logistical considerations and cost-effectiveness to optimize patient outcomes.
    Keywords:  Adoptive cell therapy - ACT; Chimeric antigen receptor - CAR; Immunotherapy; T cell Receptor - TCR; Tumor infiltrating lymphocyte - TIL
    DOI:  https://doi.org/10.1136/jitc-2025-013396
  10. Mol Ther. 2026 Jan 10. pii: S1525-0016(26)00008-0. [Epub ahead of print]
      Chimeric antigen receptor (CAR) T cell therapy achieves durable remissions in hematological malignancies, yet its success against solid tumors is blunted in part by the tumors' highly immunosuppressive microenvironment. Fourth-generation "armored" CAR T cells are engineered to secrete pro-inflammatory molecules to counteract this barrier. Here, we engineered TnMUC1-targeted CAR T cells that constitutively secrete either single-chain interleukin-12 (scIL-12) or single-chain interleukin-23 (scIL-23). Both cytokine-armored CAR T cell formats improved effector function in vitro, increasing interferon-gamma production and cytotoxicity compared with their unarmored counterparts. scIL-12- and scIL23-secreting CAR T cells significantly delayed tumor growth and prolonged survival in mouse xenograft models of human breast and prostate cancer, while scIL-23 secretion led to increases in vivo persistence and retention of early differentiation states. These findings nominate scIL-23 armoring as a promising strategy to extend CAR T cell therapy to solid tumors.
    DOI:  https://doi.org/10.1016/j.ymthe.2026.01.007
  11. Cancer Lett. 2026 Jan 13. pii: S0304-3835(26)00020-0. [Epub ahead of print]640 218257
      Chimeric antigen receptor T-cell (CAR-T) therapy has achieved unprecedented success in hematological malignancies but faces formidable challenges in solid tumors. These limitations include severe "on-target, off-tumor" toxicity, antigen heterogeneity, and the immunosuppressive tumor microenvironment, where the dense extracellular matrix acts as a physical barrier hindering T-cell infiltration. To address these hurdles, this review proposes a comprehensive Efficacy, Safety, and Accessibility (ESA) framework for engineering next-generation "Smart" CAR-T cells. We explore the implementation of programmable Boolean logic gates (AND, OR, NOT) and conditional activation systems (e.g., synNotch, focused ultrasound) that allow T cells to compute antigen patterns and precisely sense tumor-specific cues. Furthermore, we examine the development of off-the-shelf allogeneic platforms that utilize advanced gene editing technologies-such as CRISPR-Cas9 and base editing-to eliminate endogenous receptors and prevent graft-versus-host disease. Crucially, we highlight the transformative potential of Artificial Intelligence/Machine Learning in accelerating the "Design-Build-Test-Learn" cycle, from optimizing single-chain variable fragment (scFv) affinity to predicting clinical toxicity risks. By integrating these multi-dimensional strategies, we outline a new paradigm in precision immunotherapy, aiming to transform CAR-T cells into intelligent, controllable, and universally accessible living drugs capable of eradicating complex solid tumors.
    Keywords:  Artificial intelligence; CAR-T; Gene editing; Solid tumors; Synthetic biology
    DOI:  https://doi.org/10.1016/j.canlet.2026.218257
  12. Curr Opin Pharmacol. 2025 Dec 22. pii: S1471-4892(25)00098-0. [Epub ahead of print]87 102602
      Osteosarcoma (OS), the most common primary malignant bone tumor, poses significant clinical challenges owing to its high metastatic potential and resistance to chemotherapy. Although Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) has made significant progress in treating hematologic malignancies, its efficacy remains limited in solid tumors, such as OS. Chimeric antigen receptor macrophages (CAR-MΦ) represent an emerging cell therapy. It possesses potent phagocytic killing capabilities and inherent immune-modulatory properties. It has the unique potential to reshape the immunosuppressive microenvironment of OS. This review systematically outlines the target selection of CAR-MΦ in OS, its dual mechanisms of direct killing and indirect immune modulation, and thoroughly explores strategies to overcome tumor heterogeneity and immune suppression using CAR-MΦ approaches. Finally, it highlights the current challenges and future development directions. This emphasizes that CAR-MΦ therapy holds promise as a key breakthrough in overcoming the treatment bottleneck for OS. It is a key driver of the shift in the therapeutic paradigm from targeting cell toxicity to reshaping the immune microenvironment.
    DOI:  https://doi.org/10.1016/j.coph.2025.102602
  13. Nat Med. 2026 Jan 15.
      B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of multiple myeloma but can cause unique toxicities, including cranial nerve palsy, parkinsonism and enterocolitis, which we refer to collectively as CAR T cell therapy-associated immune-related adverse events (CirAEs). Among 198 patients treated with ciltacabtagene autoleucel or idecabtagene vicleucel (June 2021-December 2024), 27 (13.6%) developed CirAEs. This included one remarkable case with three distinct CirAEs in association with an extreme CD4+ CAR T cell expansion (peak lymphocytes: 197 × 103 per microliter), which was abrogated in vitro by CCR5 inhibition. CirAEs were associated with significantly higher non-relapse mortality (hazard ratio = 5.2, P = 0.006), and independent risk factors included ciltacabtagene autoleucel (odds ratio = 4.5, P = 0.058), peak absolute lymphocyte count ≥ 2.4 × 103 per microliter in the first 14 days post-infusion (odds ratio = 4.3, P < 0.001) and apheresis CD4:CD8 ratio > 1 (odds ratio = 2.6, P = 0.048). We identified marked CD4+ CAR T cell infiltration in all available CirAE tissues, including cerebrospinal fluid during neurologic CirAEs, implicating CD4+ CAR T cell therapy as a key mediator of these toxicities.
    DOI:  https://doi.org/10.1038/s41591-025-04121-8
  14. Mol Ther. 2026 Jan 10. pii: S1525-0016(26)00002-X. [Epub ahead of print]
      Restoring immune tolerance by engineered regulatory T cell (Treg) therapy is a promising strategy to treat patients suffering from autoimmune and inflammatory diseases. However, in many of these conditions, relevant disease-driving antigens are unknown. Therefore, suitable target (auto-)antigens for antigen-specific Treg cell therapy are rarely available. We present a novel artificial immune biosensor for Treg cells that circumvents this limitation by targeting the immune costimulatory protein CD40-ligand (CD40L), transiently expressed by activated T cells. The artificial immune receptor (AIR) comprises a CD40-derived extracellular binding domain, an intracellular costimulatory signaling domain and a T cell receptor signaling domain of the CD3-ζ chain. After interaction with its membrane-bound ligand, this synthetic receptor triggers a TCR-like activation program in Treg cells including induction of Treg effector molecules and cell proliferation. In a mouse model of graft-versus-host disease (GvHD), transfer of CD40-AIR Treg cells significantly improved survival and demonstrated immune control of the alloantigen-reactive T cell compartment. Expression and signaling of the corresponding human CD40-AIR illustrate the potential for translating this concept. Engineering Treg cells with a CD40L-targeting sensor, that detects activated T cells presents a promising therapeutic approach for a broad range of T cell mediated inflammatory diseases.
    DOI:  https://doi.org/10.1016/j.ymthe.2026.01.002
  15. Handb Clin Neurol. 2026 ;pii: B978-0-323-90887-0.00016-X. [Epub ahead of print]214 125-142
      Over the last three decades, immunotherapies targeting T cells, cytokines, and intracellular molecules have been explored extensively in clinical trials in multiple sclerosis (MS). These studies resulted in the approval of several therapies for the treatment of relapsing-remitting MS, and secondary and primary progressive MS. However, many treatment approaches were unsuccessful but provided important insights into pathomechanisms driving disease activity and progression in MS. Additional treatment strategies are currently evaluated in phase II and III trials in MS and are likely to improve the treatment of relapsing and progressive MS in the future. Some of the established treatment strategies in MS paved the way for the development of treatment strategies in other autoimmune diseases of the central nervous system, in particular neuromyelitis optica spectrum disorders (NMOSD) and myelin-oligodendrocyte glycoprotein-associated disorders. As a result, the first drugs for the treatment of NMOSD were recently approved and are now available to alter the course of this disease. Overall, T cell and cytokine-targeting treatment approaches have proven less successful in neuroinflammatory diseases than strategies targeting B cells. A better understanding of the pathomechanisms underlying MS and related diseases will facilitate the successful development of specific therapies targeting T cells, cytokines, and intracellular molecules in the future.
    Keywords:  Antigen-based therapy; Cytokine; Immunotherapy; Intracellular signaling; Multiple sclerosis; T cell
    DOI:  https://doi.org/10.1016/B978-0-323-90887-0.00016-X
  16. Regul Toxicol Pharmacol. 2026 Jan 12. pii: S0273-2300(26)00005-X. [Epub ahead of print] 106032
      Advanced therapeutics-including cell and gene therapies, antibody-drug conjugates, and RNA-based medicines-present unique in vivo pharmacology, safety, and translational challenges that require tailored nonclinical programs aligned with global regulatory expectations. This review synthesizes best practices for designing IND/CTA-enabling studies, integrating biodistribution, pharmacokinetics/pharmacodynamics, immunogenic assessment, safety pharmacology, toxicology, and dose selection into a cohesive strategy. Regulatory frameworks from the FDA, EMA, and PMDA emphasize early engagement, modality-specific risk assessment, and harmonization through ICH guidance (e.g., S12). Key recommendations include using relevant animal models, novel analytical methods, and conservative first-in-human dosing to mitigate translational uncertainties. Distinct considerations for oncology versus non-oncology indications are highlighted, reflecting differing risk tolerances and data requirements. Case studies of clinical holds and successful submissions underscore the importance of anticipating regulatory concerns, ensuring manufacturing readiness, and implementing robust risk mitigation. By adopting these integrated scientific and regulatory strategies, developers can streamline translation from preclinical studies to human trials, ultimately accelerating the delivery of safe, effective advanced therapies.
    DOI:  https://doi.org/10.1016/j.yrtph.2026.106032
  17. bioRxiv. 2026 Jan 09. pii: 2026.01.09.696281. [Epub ahead of print]
      B7-H3 is a cell surface protein overexpressed in many solid tumors and an attractive target for chimeric antigen receptor (CAR) T cell therapy. The most clinically advanced B7-H3 CARs are derived from murine monoclonal antibodies (mAbs) 376.96 and MGA271, which are now in phase 1/11 trials. However, non-human mAb sequences can provoke immune responses, leading to CAR T-cell rejection and therapeutic failure. Although scFv humanization reduces this risk, residual foreign residues within the variable domains remain. To overcome this limitation, we used in vitro phage display to generate fully human B7-H3-specific scFvs for CAR design. In pancreatic cancer, neuroblastoma, and glioblastoma xenograft models, CAR T cells incorporating the lead human binder Y111 were well tolerated and demonstrated superior antitumor activity compared with 376.96- and MGA271-based CARs. Y111 CAR treatment induced complete responses, tumor rejection, and significant survival benefits, identifying Y111 as a promising fully human B7-H3 CAR for solid tumors.
    DOI:  https://doi.org/10.64898/2026.01.09.696281
  18. Blood. 2026 Jan 16. pii: blood.2025030872. [Epub ahead of print]
      Chimeric antigen receptor T-cells (CAR T) are a major treatment advance for many patients with haematological malignancies, especially those with disease that has relapsed or is refractory to chemotherapy. However, currently approved commercial CAR T-cells require highly specialised manufacturing processes that contribute to high costs and limit their widespread use. In many countries, positive reimbursement recommendations by health technology assessment (HTA) bodies enable patient access to CAR T therapies. We performed a cross-sectional analysis of HTA evaluations of commercial CAR T therapies among G20 member countries plus three G20 invitees (Spain, Singapore, Switzerland) through 1 August 2025. Across the 18 CAR T-cell product-indication pairs with current FDA approval, we analysed HTA review documentation to ascertain the timing and rationale for a positive or negative recommendation. Fourteen countries with public HTA data were included in our analysis. Forty-eight percent of CAR T-indication pairs (122/252) are currently recommended for reimbursement by public health systems. The median time from FDA approval to HTA decision was 1·54 years (interquartile range 1·15-2·59 years). Common barriers to CAR T cost-effectiveness cited in HTA reports included single-arm trial designs, small study populations, and immature data regarding survival, safety, and quality of life. Our findings demonstrate substantial global disparities in access to CAR T treatments even among high- and upper middle-income countries, highlighting the urgent need for both scientific and policy approaches to reduce costs and improve access to these impactful therapies.
    DOI:  https://doi.org/10.1182/blood.2025030872
  19. Acta Oncol. 2026 Jan 14. 65 22-31
       BACKGROUND AND PURPOSE: In the current landscape of tumour-agnostic oncology drugs receiving European Medicines Agency (EMA) authorisation, Health Technology Assessment (HTA) bodies face challenges in assessing these innovative drugs. Due to these products' non-randomised, single-arm nature, uncertainty exists regarding their real-world benefit. In the Netherlands, the Drug Access Protocol (DAP), a programme developed by oncologists, insurers and the healthcare public institute, aims to provide an innovative solution to address this uncertainty. This study aims to investigate the key characteristics, enablers and challenges of the programme by exploring stakeholders' perceptions. Patient/material and methods: A qualitative, semi-structured interview study was conducted. A supporting interview guide was drafted using available literature and a flowchart figure to illustrate the process. Interviews were conducted with market authorisation holders (MAHs) who participated in the programme, the insurer, the DAP study management and the DAP's governance committee. Recorded interviews were transcribed, pseudonymised and subsequently coded using NVivo software. Inductive thematic analysis was used to identify common themes, enablers and challenges for participating in the programme.
    RESULTS: In total, eight organisations were interviewed. Although MAHs indicated several enablers (e.g. providing patient access, collecting real-world data), several challenges (e.g. the lack of transparency) lead to questions regarding the feasibility of the programme. Health insurers acknowledge these outcomes and expect products that obtain regular reimbursement to serve as an example.
    INTERPRETATION: As the Drug Access Protocol may be a promising solution to mitigate uncertainties for healthcare decision-makers, implementation challenges can hamper its feasibility. Addressing these challenges could realise the potential of such programmes.
    DOI:  https://doi.org/10.2340/1651-226X.2026.45000
  20. Mil Med Res. 2026 Jan 12. 12(1): 95
      The cytokine storm, a life-threatening systemic inflammatory syndrome, is the primary driver of multiorgan failure in different clinical situations, including severe infections, autoimmune diseases, chimeric antigen receptor (CAR) T cell immunotherapy for cancer, and genetic syndromes. This review focuses primarily on cytokine storms triggered by severe infections such as viral pneumonia and bacterial sepsis, and explores the underlying mechanisms of cytokine storms and potential therapeutic interventions. Cytokine storms are characterized primarily by the excessive release of proinflammatory cytokines, which are triggered by pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and PANoptosis, all of which activate immune signaling cascades. Amplification mechanisms involve positive feedback loops and the failure of negative feedback mechanisms, leading to uncontrolled inflammation. Like a pyrrhic victory, the excessive activation of the immune system eliminated invading pathogens but caused catastrophic damage due to multiple organ dysfunction syndrome (MODS), turning the life-saving response into a life-threatening war. Therapeutic strategies, including cytokine antagonists, Janus kinase (JAK) inhibitors, caspase inhibitors, glucocorticoids, and blood purification therapies, aim to interrupt the self-amplifying cycle of inflammation that propagates organ injury, thereby reducing MODS and mortality. Challenges include optimizing the treatment timing and patient stratification. Future research should focus on combination therapies and personalized medicine based on the heterogeneity of infections and sepsis. Advances in multiomics and targeted therapies provide new hope for managing infections and sepsis.
    Keywords:  Cytokine storm; Inflammatory response; Multiple organ dysfunction syndrome; Sepsis; Severe infection
    DOI:  https://doi.org/10.1186/s40779-025-00678-0
  21. Immunol Invest. 2026 Jan 11. 1-36
       INTRODUCTION: Colorectal Cancer has been a significant health issue at a global level in terms of increasing incidence, high metastatic capacity, and inadequate treatment reactions in most patient groups. Though chemotherapy and targeted agents have given better survival chances, resistance to treatment, avoidance of the immune system as well as systemic toxicity still limit long-term efficacy. Immunotherapeutic strategies have developed as effective methods in the past few years to address these shortomings.
    METHODS: A comprehensive literature search was conducted across different electronics databases including Web of Science, PubMed, Scopus, and ScienceDirect utilizing keywords colorectal cancer immunotherapy, PD-1 / PD-L1, CAR-T cells, viral vector vaccines, carcinoembryonic antigen alone and in combinations.
    RESULTS: PD-1/PD-L1, CTLA-4, immune checkpoint inhibitors have shown long-term responses, especially in mismatch repair-deficient and microsatellite instability-high tumours, and cell-based therapies such as CAR -T cells and dendritic cell vaccines provide other opportunities of personalised immune modulation.
    DISCUSSION: This critical review summarizes the current developments in terms of immunotherapy and interventions of CRC with a focus on the mechanistic understanding of the issue, clinical outcomes, and combinatorial strategies aimed to improve antitumor immunity and surmount therapy resistance. Specific attention is paid to the optimization of the checkpoint blockade, innovations with vaccines and CAR-T engineering to accumulate and release tumor-specific cells and control the microenvironment. Finally, key translational challenges current clinical trials, and future perspectives are identified to promote the development of the next-generation multimodal therapies in the efficient and customized management of CRC.
    Keywords:  CAR-T cells; Colorectal cancer immunotherapy; PD-1/PD-L1; carcinoembryonic antigen; dendritic cell vaccines; viral vector vaccines
    DOI:  https://doi.org/10.1080/08820139.2026.2613047
  22. Value Health. 2026 Jan 14. pii: S1098-3015(26)00002-1. [Epub ahead of print]
       OBJECTIVES: To evaluate methodological challenges and regulatory considerations of indirect treatment comparisons (ITCs) with the analysis of French Transparency Committee (TC) decisions and international health technology assessment guidelines.
    METHODS: We conducted a pragmatic review of ITC guidelines from major health technology assessment bodies and analyzed 138 TC opinions containing 195 ITCs published between 2021-2023. We extracted data on ITC methodology, therapeutic areas, acceptability, and limitations expressed by the TC.
    RESULTS: ITC submissions increased by 44.7% over the study period, but only 13.3% of these comparisons influenced TC decision-making. ITCs were more frequently accepted in genetic diseases (34.4%) compared to oncology (10.0%) and autoimmune diseases (11.1%). Methods using individual patient data showed higher acceptance rates (23.1%) than network meta-analyses (4.2%). Main limitations included heterogeneity/bias risk (59%), lack of data (48%), statistical methodology issues (29%), study design concerns (27%), small sample size (25%), and outcome definition variability (20%). When ITCs were the primary source of evidence, the proportion of important clinical benefit was lower (60.9% vs. 73.4%) than when randomized controlled trials were available.
    CONCLUSIONS: While ITCs are increasingly submitted, particularly where direct evidence is impractical, their influence on reimbursement decisions remains limited. There is a need for clear and accessible guides so manufacturers can produce clearer and more robust ITCs that follow regulatory guidelines, from the planning phase to execution.
    Keywords:  External control arm; Health technology assessment; Indirect treatment comparison; Regulatory guidelines; Reimbursement decision
    DOI:  https://doi.org/10.1016/j.jval.2025.12.013
  23. Protein Pept Lett. 2026 Jan 08.
      Messenger RNA (mRNA) has gained increasing attention as a valuable tool to cure various human diseases, particularly malignant tumors. Such growing interest has been triggered largely by the phenomenal clinical success of mRNA vaccines developed using lipid nanoparticle (LNP) technology against COVID-19. mRNA may be used to produce cancer immunotherapies in numerous different ways, including cancer vaccines to induce or enhance immunity to tumor-specific antigens (TSAs) or tumor-associated antigens (TAAs). mRNA can also be used to adoptively transfer T-cells for the expression of antigen receptors, such as chimeric antigen receptors (CARs), therapeutic antibodies, and immunomodulatory proteins to re-engineer the tumor microenvironment. However, the therapeutic potential of mRNA-based cancer immunotherapy is not fully utilized due to a few limitations, such as mRNA instability, production of immunogenicity, and a lack of efficient in-vivo delivery methods. This review provides an overview of the current advancements and future directions of mRNA-based cancer therapies, including various delivery routes and therapeutic platforms. It addresses the mechanistic basis of mRNA cancer vaccines, non-replicating and self-amplifying mRNA, as well as their clinical development, personalized vaccines, and applications of mRNA for encoding antigen receptors, antibodies, and immunomodulatory proteins. Moreover, the review addresses nanoparticle-based platforms, such as lipid nanoparticles (LNPs), polymeric nanoparticles, and peptide-based nanoparticles, all used to improve the therapeutic effectiveness of mRNA-based drugs by improving their targeted delivery to tissues. This review aims to provide insights into the use of state-of-the-art mRNA-based cancer immunotherapy.
    Keywords:  Lipid nanoparticles (LNPs); adoptive T-cell therapy; chimeric antigen receptors (CARs); nanoparticle delivery systems; non-replicating mRNA; self-amplifying mRNA; tumor-associated antigens (TAAs).
    DOI:  https://doi.org/10.2174/0109298665402963251022054441
  24. J Nanobiotechnology. 2026 Jan 17.
      Extracellular vesicles (EVs) are emerging as naturally bioactive nanomaterials with intrinsic biocompatibility and targeting potential. Recent integration of machine learning (ML) into EV research has accelerated advances in molecular profiling, structure-function prediction, and rational design of vesicle-based therapeutics. Yet, the inherent complexity and heterogeneity of EV populations pose major analytical challenges. Concurrently, machine learning is revolutionizing biomedical science by uncovering patterns in high dimensional, multimodal datasets. In EV research, ML has enabled major advances across automated imaging, multi omics integration, disease classification, therapeutic engineering, and standardization. This review presents a comprehensive synthesis of ML-enabled EV studies, organized by data modality (imaging, omics, cytometry), algorithmic paradigm (CNNs, random forests, autoencoders, GNNs), and translational application (diagnosis, prognosis, drug delivery, manufacturing QC). Unlike prior reviews that have typically considered EV biology and AI methods in relative isolation, we introduce a unified three-axis taxonomy that explicitly links EV data modalities, machine learning architectures, and clinical use-cases, thereby providing a structured map of the field. We discuss key technical barriers including data sparsity, batch variability, and model explainability and spotlight frontier developments such as federated learning, self-supervised models, and real-time EV analytics. At the nexus of computational intelligence and nanomedicine, ML-enhanced EV platforms are rapidly progressing from fragmented innovations to clinically actionable systems. This review offers a roadmap for advancing AI-integrated EV technologies in cancer precision medicine.
    Keywords:  AI driven materials design; Bioinspired nanomaterials; Extracellular vesicles (EVs); Machine learning in nanomedicine; Smart nanotherapeutics; Targeted drug delivery platforms
    DOI:  https://doi.org/10.1186/s12951-025-03952-4
  25. Exp Hematol Oncol. 2026 Jan 11. 15(1): 7
      Cancer continues to pose a significant issue to public health. Despite the considerable advancements in popular therapies such as surgery, radiation, chemotherapy, targeted therapy, and immunotherapy, a substantial number of patients continue to suffer from cancer due to severe treatment resistance. As a result, it is imperative to have a deeper understanding of the mechanisms behind cancer growth and therapy resistance. Ferroptosis, an iron-dependent form of cell death characterized by excessive lipid peroxidation, has recently been described, attracting heightened interest in its implications in cancer. Ferroptosis offers a new conceptual framework for understanding cancer progression. Some treatments function via regulating ferroptosis, and the tough insensitive to various therapies also involves ferroptosis resistance. Hence, targeting ferroptosis may benefit the cancer treatments. Extracellular vesicles (EVs) are essential mediators in cell-to-cell communications and are significantly impacted by environmental or cellular stress. The relationship between EVs and ferroptosis has recently been steadily demonstrated, and it has also been possible to use EVs to target ferroptosis to treat cancer. We present a novel perspective on cancer by reexamining the existing knowledge of ferroptosis and EVs in this disease. This includes a comprehensive overview of the relationships between ferroptosis and EVs and their therapeutic applications, focusing on contemporary ferroptosis-targeting EVs in the context of cancer.
    Keywords:  Cancer treatment; Cell communication; Extracellular vesicles; Ferroptosis
    DOI:  https://doi.org/10.1186/s40164-025-00736-2
  26. Handb Clin Neurol. 2026 ;pii: B978-0-323-90887-0.00003-1. [Epub ahead of print]214 47-64
      B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurologic disorders, acting, in addition to their autoantibody-secreting role, as antigen-presenting cells but also as sensors, coordinators, and regulators of the immune response. B cells can regulate the immune response, including T-cell activation through antigen presentation, production of proinflammatory cytokines (either as a bystander activation or suppression), and contribution to ectopic lymphoid aggregates. Such important functions make therapeutic depletion of B cells an attractive treatment strategy. The last decade, anti-B-cell therapies targeting B-cell surface molecules, have evolved into a rational approach for successfully treating autoimmune neurologic disorders, even when T cells seem to be the main effector cells, providing an invaluable therapeutic criterion for appreciating the key role of B cells in neurologic autoimmunities. The chapter is focused on the basic aspects of B-cell biology, addresses the different roles of B cells and autoantibodies in the pathogenesis of autoimmune and inflammatory neurologic disorders and highlights how the currently available or in the developmental stage anti-B-cell therapeutics exert their action. It specifically examines the autoantibodies of different IgG-isotypes and IgG-subclasses stressing the uniqueness of IgG4-neuroautoimmunities, and summarizes the current status of the rapidly evolving B-cell therapeutics, including CD19-CAR-T cell therapies, in multiple sclerosis, neuromyelitis-spectrum disorders, autoimmune encephalitis, stiff-person syndrome spectrum disorders, chronic autoimmune neuropathies, myasthenia gravis, and inflammatory myopathies.
    Keywords:  Autoantibodies; Autoimmunity; B cells; Immunotherapy; Neurologic disorders; Rituximab
    DOI:  https://doi.org/10.1016/B978-0-323-90887-0.00003-1
  27. J Evid Based Med. 2026 Jan 14. e70107
      Cytomegalovirus (CMV) is an increasingly recognized complication of chimeric antigen receptor T-cell (CAR-T) and bispecific antibody (BsAb) therapies for hematologic malignancies, driven by therapy-related immunosuppression and cumulative exposure to lymphodepleting or steroid regimens. Given China's high adult CMV IgG seroprevalence (>90%), baseline risk, interpretation of low-level DNAemia, and operational thresholds differ from low-seroprevalence settings, requiring context-specific guidance. This China-adapted, evidence-graded consensus was developed by a multidisciplinary panel from major centers using a modified Delphi process and Oxford Centre for Evidence-Based Medicine levels to translate international guidance into a high-seroprevalence setting. Recommendations prioritize early risk stratification and pragmatic surveillance. We advise routine CMV monitoring by real-time quantitative PCR during the first 30 days after therapy, with risk-adapted extension thereafter. Interpretation and treatment triggers are anchored to WHO-traceable IU/mL and specified by specimen matrix to support comparability across assays. Consideration of prophylaxis is proposed for well-defined high-risk subgroups, acknowledging the need for prospective validation. Syndrome-based diagnostic and treatment algorithms are provided for tissue-invasive disease, including CMV pneumonia and encephalitis, with guidance on antiviral induction, step-down, and monitoring for virologic response and drug toxicity. This consensus explicitly adapts international recommendations to China's epidemiology, assay practice, and drug accessibility. By standardizing prevention, surveillance, and management in CAR T-cell and BsAb recipients, this consensus aims to lower non-relapse mortality and improve long-term outcomes. Priority research needs include harmonized viral-load thresholds, validation of risk-adapted prophylaxis strategies, and studies that clarify the significance of low-level DNAemia in this population.
    Keywords:  CAR‐T therapy; Delphi consensus; bispecific antibodies; cytomegalovirus; guideline adaptation; infection management
    DOI:  https://doi.org/10.1111/jebm.70107
  28. Cureus. 2025 Dec;17(12): e99102
      This study aims to analyze the literature published regarding nano-oncology and, more specifically, global trends concerning nanoparticles and nanotubes from 2003 to 2025. This bibliometric analysis gathered data from the Web of Science Core Collection, incorporating keywords such as oncology, nanotechnology, nanomedicine, nanoparticles, and nanotubes. With the retrieved data visualized in the VOSViewer program and Web of Science Core Collection, the primary focus was on keywords, countries, and organizations, from 1,465 total documents. Analysis indicates that research has increased recently because of the development of nanotechnologies, particularly through drug delivery and imaging mechanisms. The United States, the People's Republic of China, and India were the most prevalent publishers, often collaborating with other countries to focus on an integrated global community with similar nanotechnological interests based on shared challenges. Overall, this analysis highlights the continuously evolving field of nano-oncology and how these advancements will reshape global cancer treatment.
    Keywords:  bibliometric analysis; cancer; nano-oncology; nanocarrier drug delivery; nanomedicine; nanoparticles; nanotechnology; nanotubes; oncology; precision technology
    DOI:  https://doi.org/10.7759/cureus.99102
  29. Handb Clin Neurol. 2026 ;pii: B978-0-323-90887-0.00023-7. [Epub ahead of print]214 3-7
      This introductory chapter describes the evolution of immunotherapies in neurology as witnessed from the late 1970s to early 1980s, when the main therapy for all autoimmune neurologic diseases was only oral and IV steroids, to the present. The growing pains, complexities, challenges, and the very slow pace by which newer immunotherapeutic options were evolving are discussed pointing out that effective new therapies started to evolve many years later in the late 1990s to 2000 with plasmapheresis, IVIg, and β-interferon as the only disease modifying therapy (DMT) for multiple sclerosis. These early therapies were, however, the impetus for a subsequent faster pace of exploring new biologics with both failures and successes that steadily led to the present impressively galloping pace of trials and approvals of various monoclonal antibodies against B cells, cytokines, complement, FcRn, and currently Bruton's Tyrosine Kinase (BTK) inhibitors across the spectrum of all autoimmune neurologic diseases collectively pointing out that neuroimmunotherapy is now a "living process" with evolving therapeutic schemes that continuously change the therapeutic algorithm. The epitome of this successfully rapidly evolving pace is highlighted by the CAR-T cell therapies, currently explored in all refractory neuro-autoimmunities, when they were not even on the list when this volume began. The chapter describes this remarkable 40-year progress and evolution on immunotherapies in every autoimmune neurologic disease, addresses what has been learnt from the success and failures in the conducted therapeutic trials or targeted therapies, and highlights the promising future as currently projected in neuroimmunotherapeutics.
    Keywords:  Autoimmune neurologic diseases; Corticosteroids; Immunotherapeutic agents; Immunotherapies; Neurology
    DOI:  https://doi.org/10.1016/B978-0-323-90887-0.00023-7
  30. BioDrugs. 2026 Jan 10.
      Gene and cell therapies have been gaining popularity with market approvals by the US Food and Drug Administration, European Medicines Agency, and other regulatory bodies. Adeno-associated viral vector gene therapies approved for rare inherited diseases and chimeric antigen receptor T-cell therapies approved as a novel modality for hematological anti-cancer therapies have led the way in a new paradigm of drug discovery and development. Previously incurable diseases such as hemophilia A and B have now been effectively treated via adeno-associated viral vector-mediated gene therapy, and chimeric antigen receptor T-cell therapies have provided cures for lymphomas in patients refractory to all previous treatments demonstrating the great promise of these agents. Immunogenicity is a major factor hampering the efficacy and eligible population of gene therapies as well as creates a safety risk for some individuals. Inherent attributes of adeno-associated viral vector gene and autologous chimeric antigen receptor T-cell therapies present a unique set of factors that can influence immunogenicity to the drug compared to widely used small-molecule or biologic drugs. This review outlines immunogenicity concerns of gene and cell therapy, and their clinical manifestations. We detail mechanisms by which these therapies can trigger innate, humoral, and cellular immunity. Additionally, we give an in-depth discussion of in silico, in vitro, and in vivo immunogenicity screening methods that have been applied in gene and cell therapy development, and the utility of each.
    DOI:  https://doi.org/10.1007/s40259-025-00756-8
  31. Int J Clin Oncol. 2026 Jan 12.
      Despite multimodal treatment options, most gastrointestinal (GI) cancers remain associated with high mortality rates and poor responsiveness to immunotherapy. The remarkable success of immune cell-based therapies in hematologic malignancies has raised interest in translating adoptive cell therapies to GI cancers. Among these approaches, natural killer (NK) cell-based therapies offer potent cytotoxicity, and a favorable safety profile. Multiple NK cell platforms are now under preclinical and clinical development, demonstrating encouraging therapeutic efficacy in GI malignancies. Nevertheless, challenges such as limited in vivo persistence, immunosuppressive tumor microenvironment (TME), and heterogeneous expression of NK cell therapy targeted antigens continue to limit therapeutic benefit. Recent advances are being explored to overcome these barriers and enhance NK cell persistence and specificity. This review summarizes recent progress in NK cell-based immunotherapy for GI cancers, highlights representative clinical trials, and discusses strategies to improve efficacy and durability. With continued innovation, NK cell-based therapy holds promise to become an essential component of the future immunotherapy landscape for GI malignancies.
    Keywords:   Adoptive cell transfer; CAR-NK cells; Cancer immunotherapy; Gastrointestinal cancers; NK cell therapy; Natural killer cells
    DOI:  https://doi.org/10.1007/s10147-025-02954-4
  32. Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 Nov 20. 56(6): 1453-1458
      Shimon Sakaguchi, a Japanese scientist, together with Mary E. Brunkow and Fred Ramsdell, American scientists, were jointly awarded the 2025 Nobel Prize in Physiology or Medicine for their pioneering discoveries in the field of peripheral immune tolerance. This review summarizes the Nobel Prize-winning research on immune tolerance and discusses the development, functions, and therapeutic applications of regulatory T cell (Treg)-based interventions. These seminal studies on immune tolerance underscore a central immunological concept-a healthy immune system relies not only on its robust capacity to eliminate pathogens and mutated cells, but also on the precise inhibitory (or "brake") and tolerance mechanisms. This concept will help deepen our understanding of key medical challenges such as autoimmune diseases, transplant rejection, and tumor immunity. It will spur the development of a series of therapeutic strategies targeting peripheral immune tolerance and Treg cells and advance research in precision immune regulation.
    Keywords:  Nobel Prize; Peripheral immune tolerance; Regulatory T cells; Review
    DOI:  https://doi.org/10.12182/20251160302
  33. Cureus. 2025 Dec;17(12): e98839
      Regulatory T-cells (Tregs) are central to peripheral immune tolerance and act as key players that sustain the immune homeostasis required for embryo receptivity, implantation, and placentation. Treg dysfunction accelerates inflammation, angiogenesis, and lesion progression in endometriosis, whereas preclinical work indicates that adoptive Treg supplementation can restrain the advancement of endometriosis‑like lesions. Using the 2025 Nobel Prize in Physiology or Medicine scientific background as a starting point, this review summarizes Treg basic biology, roles in reproductive immunology, the pathophysiology of immune‑mediated infertility and endometriosis, and therapeutic prospects centered on Treg induction and supplementation.
    Keywords:  cell therapy; endometriosis; immune tolerance; implantation; low‑dose il‑2; recurrent implantation failure; regulatory t-cells
    DOI:  https://doi.org/10.7759/cureus.98839
  34. J Hematol Oncol. 2026 Jan 11. 19(1): 12
      The advent of next-generation high-throughput sequencing and precision medicine has allowed the identification of recurrent genetic events of vital interest for leukemic cells and for the management of patients with leukemia, since it has a direct impact on prognosis and therapeutic stratification. The precise cytogenetic characterization of these diseases has rapidly enabled the development of innovative therapeutic strategies to improve outcomes and limit toxicities. New targeted therapies, including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and chimeric antigen receptor T cells (CAR-T cells) represent a broad therapeutic arsenal now available in everyday practice. The growing number of treatments means that many possibilities of drugs and combinations can be used to offer new lines of therapy in cases of refractory disease or relapse, but also in frontline treatment. This review provides a broad overview of pathogenic mechanisms and therapies (including targeted therapies, immunotherapy and RNA-based therapy) and gathers the main research progress in the field of leukemia.
    Keywords:  Antisense oligonucleotides; Immunotherapy; Leukemia; Targeted therapy
    DOI:  https://doi.org/10.1186/s13045-025-01775-2
  35. Eur J Med Res. 2026 Jan 13.
       OBJECTIVES: Neuroblastoma (NB) is a common and life-threatening pediatric solid tumor with a poor prognosis, especially in high-risk patients. Although anti-disialoganglioside GD2 (GD2) monoclonal antibodies improve survival, relapse and resistance remain major challenges. This study aimed to evaluate the safety and efficacy of GD2-targeted chimeric antigen receptor (CAR)-T-cell therapy in NB patients.
    METHODS: A literature search was conducted in PubMed, Embase, Scopus, and Web of Science until September 30, 2025. Eligible studies were clinical trials that evaluated the efficacy and safety of GD2-targeted CAR-T-cell therapy in NB patients. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. The random-effects meta-analysis model was used to calculate pooled amounts.
    RESULTS: Eight studies that included 146 patients with NB were included. The pooled complete response (CR) rate was 39.57% (21.17-57.96), and the partial response (PR) rate was 15.83% (5.02-30.45). Additionally, the rates of progressive disease (PD) and stable disease (SD) were 20.9% (3.06-46.67) and 30.76% (12.81-51.91), respectively. The most common "any grade" adverse events (AEs) was anemia, at 97.43% (81.51-100), and the most common "grade ≥ 3" AEs was neutropenia, at 93.46% (72.65-100). Subgroup analyses revealed that CAR-T-cell generation and its components influenced efficacy and safety.
    CONCLUSION: CAR-T-cell therapy targeting the GD2 antigen is promising for treating NB. However, its efficacy is moderate, and treatment can lead to hematologic toxicities such as anemia, neutropenia, and thrombocytopenia, which require careful monitoring.
    Keywords:  CAR-T-cell therapy; Chimeric antigen receptor; GD2; Immunotherapy; Neuroblastoma
    DOI:  https://doi.org/10.1186/s40001-025-03764-0
  36. Croat Med J. 2026 Jan 05. 66(6): 436-445
       AIM: To systematically review the latest pharmacoeconomic evidence regarding the costs associated with myasthenia gravis (MG) care and treatment.
    METHODS: We searched the National Health Service Economic Evaluation Database and PubMed for articles in English from any country reporting health economic analyses of pharmacological treatments, hospitalization, or surgical procedures related to MG.
    RESULTS: The study included 31 articles showing a considerable variability in the costs and cost-effectiveness of MG treatments across regions, therapies, and health care settings. Traditional therapies such as plasma exchange (PLEX) and intravenous immunoglobulin (IVIg) differ notably in cost, with PLEX generally being less expensive. Newer clinically effective treatments such as efgartigimod and eculizumab raise concerns about their economic sustainability, whereas rituximab might be a more affordable alternative in certain contexts.
    CONCLUSION: Future research should compare cost-effectiveness across health care systems, incorporating local pricing and reimbursement, and collecting real-world data.
  37. Cureus. 2026 Jan;18(1): e101460
      Introduction Renal complications are increasingly recognized after chimeric antigen receptor (CAR) T-cell therapy. We evaluated the incidence and severity of acute kidney injury (AKI), the prevalence of electrolyte disturbances, and clinical factors associated with AKI in adult patients with hematological malignancies. Methods We retrospectively reviewed all adult patients with hematological malignancies who received CAR T-cell therapy at a single tertiary center between November 2023 and April 2025. Baseline demographics, comorbidities, prior therapies, and post-infusion events were collected from electronic medical records. AKI was defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines based on serum creatinine (Cr) levels. Electrolyte disturbances (sodium, potassium, and phosphate) occurring within 100 days post-infusion were recorded. Data were analyzed using R statistical software (version 4.5.1). Continuous variables are presented as the mean ± SD or median (IQR). Groups were compared using t-tests, Wilcoxon rank-sum tests, and Fisher's exact tests. Associations between AKI and patient characteristics were assessed using logistic regression. Hospitalization outcomes were evaluated using Kaplan-Meier and Cox proportional hazards models. A p-value < 0.05 was considered statistically significant. Results This study included 16 patients (mean age: 56.7 ± 17.7 years; 50% male), 25% of whom developed AKI (all stage 1). Pre-existing chronic kidney disease (CKD), baseline Cr ≥75 μmol/L, and diabetes mellitus showed the strongest associations with AKI. Electrolyte disturbances were common, particularly potassium and phosphate abnormalities. AKI was not significantly associated with ICU admission, longer hospitalization, or early mortality. Conclusion In this cohort, renal events after CAR T-cell therapy were mainly mild. Pre-existing CKD and diabetes mellitus were associated with an increased risk of AKI. Therefore, we suggest close monitoring of kidney function and other risk factors (such as nephrotoxic medications, contrast exposure, and dehydration) during treatment. Further studies with larger cohorts and longer follow-up are required to clarify the mechanisms of renal impairment and better assess outcomes.
    Keywords:  acute kidney injury; car-t therapy; electrolyte disorders; hematologic malignancies; nephrotoxicity
    DOI:  https://doi.org/10.7759/cureus.101460
  38. Curr Gastroenterol Rep. 2026 Jan 14. 28(1): 5
       PURPOSE OF REVIEW: This review summarizes the history and current landscape of fecal microbiota transplantation (FMT), with an emphasis on use of the therapy for Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). We clarify indications, evidence, and current recommendations for FMT-highlighting major advances and minor setbacks that have led to the state of FMT in 2025.
    RECENT FINDINGS: After decades of steady progress, the U.S. Food and Drug Administration (FDA) approved the first FMT-based therapies: fecal microbiota, live-jslm and fecal microbiota spores, live-brpk-in 2022 and 2023, respectively. The 2024 American Gastroenterological Association (AGA) Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases made specific recommendations for conventional FMT and these FDA-approved therapies for multiple CDI presentations, as well as for IBD and IBS. Conventional FMT remains an option for CDI; however, OpenBiome's halt of shipped, frozen FMT preparations on December 31, 2024, has made access more challenging in 2025. Although first reported almost seventy years ago, extensive efforts over the last two decades have placed FMT in routine algorithms for many patients with CDI. While understanding of the intestinal microbiome's role in other gastrointestinal conditions is expanding, and FMT may modulate these pathways, additional evidence is needed before FMT becomes routine outside CDI.
    Keywords:   Clostridioides difficile ; Fecal microbiota transplantation; Inflammatory bowel disease; Irritable bowel syndrome; Recurrent Clostridioides difficile infection; Severe or fulminant Clostridioides difficile infection
    DOI:  https://doi.org/10.1007/s11894-025-01030-1
  39. Biomol Biomed. 2026 Jan 16.
      Autoimmune diseases are becoming increasingly prevalent and can cause multi-organ damage through dysregulated immune responses to self-antigens. This review aims to summarize the roles of annexin family proteins and annexin autoantibodies in the mechanisms of autoimmune diseases, as well as their potential diagnostic and therapeutic applications. A targeted PubMed search conducted on August 31, 2025, utilized annexin- and disease-related terms without year restrictions, focusing on English-language, peer-reviewed studies involving humans or recognized animal models. Evidence suggests that Annexin A1 (ANXA1) and formyl peptide receptor 2 (FPR2) signaling can influence inflammatory and T-cell responses. Additionally, Annexin A2 (ANXA2) is associated with organ-targeted injury, such as lupus nephritis (LN) in systemic lupus erythematosus (SLE), through its interactions with anti-double-stranded DNA antibodies (anti-dsDNA). Annexin A5 (ANXA5) serves as an anticoagulant phospholipid "shield," which can be compromised by antiphospholipid antibodies (aPLs), contributing to thrombosis and obstetric complications in antiphospholipid syndrome (APS) and increasing vascular risk in SLE. In rheumatoid arthritis (RA), ANXA1 exhibits context-dependent effects, while ANXA2 promotes synovial proliferation, invasion, and angiogenesis. Dysregulation of annexins has also been observed in primary Sjögren's syndrome (pSS), multiple sclerosis (MS), and systemic sclerosis (SSc). Additionally, the emerging utility of anti-ANXA1, anti-ANXA2, and anti-ANXA5 autoantibodies for phenotyping and risk stratification, including in seronegative antiphospholipid syndrome (SNAPS), highlights their clinical relevance. Overall, annexins and their autoantibodies represent promising biomarkers and therapeutic targets; however, the heterogeneity of assays and the limited availability of prospective multicenter data currently hinder clinical translation.
    DOI:  https://doi.org/10.17305/bb.2026.13546
  40. Microb Pathog. 2026 Jan 14. pii: S0882-4010(26)00025-2. [Epub ahead of print] 108299
      Chronic non-communicable diseases (CNCDs) extend beyond the metabolic domain, affecting neurological, cardiovascular, rheumatologic, respiratory, gastrointestinal, and renal systems. These conditions share underlying mechanisms involving low-grade inflammation, immune dysregulation, and metabolic imbalance, often influenced by gut microbiota alterations. The microbiota mediates systemic effects via microbial metabolites, immune modulation, and barrier integrity. Recent research has highlighted that these microbiota-mediated interactions are not unidirectional but involve complex bidirectional signaling between the gut and distal organs. Microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and tryptophan-derived indoles are messengers that influence neuroinflammation, endothelial function, immune responses, and even behavior. The gut microbiota is now viewed as an endocrine-like organ that can modulate systemic physiology. Understanding these pathways has opened new avenues for treating systemic diseases by modulating the gut ecosystem, offering novel perspectives for therapeutic intervention in conditions that were traditionally managed without considering microbiota.
    Keywords:  chronic non-communicable diseases; dysbiosis; gut microbiota; immune system; inflammation; systemic disorders
    DOI:  https://doi.org/10.1016/j.micpath.2026.108299