bims-carter Biomed News
on CAR-T Therapies
Issue of 2025–05–18
twenty-six papers selected by
Luca Bolliger, lxBio
  1. From lab to lifesaver: the rise of CAR T-cell therapy in oncology.
  2. [The current role of CAR-T cell treatment in lymphoma therapy: focus on diffuse large cell lymphoma and mantle cell lymphoma.]
  3. [Enhancing CAR-T/CAR-NK Cells through by Cytokine Signaling].
  4. CAR-T cell therapy for juvenile-onset autoimmune diseases: a promising future?
  5. Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies.
  6. Prospects for γδ T cells and chimeric antigen receptor γδ T cells in cancer immunotherapy.
  7. Toxicities Associated with CAR-T Cell Therapies.
  8. An Analysis of Monitoring Solutions for CAR T Cell Production.
  9. The role of single cell transcriptomics for efficacy and toxicity profiling of chimeric antigen receptor (CAR) T cell therapies.
  10. mRNA lipid nanoparticles in CAR-T therapy: a novel strategy to improve efficacy.
  11. Chimeric antigen receptor-macrophages: Emerging next-generation cell therapy for brain cancer.
  12. Mechanostimulatory Platform for Improved CAR T Cell Immunotherapy.
  13. A Literature Review on the Impact of the Gut Microbiome on Cancer Treatment Efficacy, Disease Evolution and Toxicity: The Implications for Hematological Malignancies.
  14. Clinical Progress in Mesenchymal Stem Cell Therapy: A Focus on Rheumatic Diseases.
  15. The Microbiome and Cancer: A Translational Science Review.
  16. Using TCR-CAR dual signaling for precise cancer targeting.
  17. Emerging trends in clinical allogeneic CAR cell therapy.
  18. Advances in T Cell-Based Cancer Immunotherapy: From Fundamental Mechanisms to Clinical Prospects.
  19. Asia's emergence in cancer immunotherapy: challenges and opportunities.
  20. Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies.
  21. Phage therapy: a promising approach for Staphylococcus aureus diabetic foot infections.
  22. Generation of T cell responses against broad KRAS hotspot neoantigens for cell therapy or TCR discovery.
  23. From Multi-Omics to Visualization and Beyond: Bridging Micro and Macro Insights in CAR-T Cell Therapy.
  24. Socioeconomic Status and Breast Cancer Treatment in the United States: Results From a Systematic Literature Review.
  25. Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families.
  26. An overview of computational methods in single-cell transcriptomic cell type annotation.
  1. J Egypt Natl Canc Inst. 2025 May 16. 37(1): 37
    From lab to lifesaver: the rise of CAR T-cell therapy in oncology.
    Shriyash S Jangavali, Pallavi B Hangargekar, Balasaheb U Gangthade, Shreya A Jadhav, Ujwal A Havelikar, Amol A Joshi.
       BACKGROUND: Recently, cancer treatment paradigms have shifted dramatically with the advent of immunotherapies, particularly chimeric antigen receptor (CAR) T-cell therapy. Despite it is revolutionary positive outcomes in treating hematologic malignancies, challenges such as severe toxicities, high treatment costs, and limited efficacy in solid tumors persist. This review highlights these limitations and the ongoing need for innovation in CAR T-cell therapy.
    MAIN BODY: This manuscript provides a comprehensive review of most current advancements in CAR T-cell therapy, with a focus on targeting its immunotherapeutic principles, modification of T cells for Targeted cancer therapy using T cells, and clinical applications. It explores the key elements of CAR T-cell therapy, containing antigen recognition domain and intracellular signaling domains, which enable T cells to interact with cancer cells and exert cytotoxic effects. The review examines approved therapies, and ongoing clinical trials, Along with obstacles like cytokine release syndrome (CRS), neurotoxicity, along antigen escape mechanisms. Furthermore, innovations in cutting-edge CAR T-cell therapies and personalized treatment approaches are discussed, together with an emphasis on improving safety and efficacy.
    CONCLUSION: The manuscript outlines the future outlook on integrating CAR T-cell therapy integrated with other treatments and exploring patient-specific approaches to revolutionize cancer care. This review aims to bridge the existing gaps in research, offering valuable insights for students and researchers in biomedical sciences and oncology.
    Keywords:  CAR T-cell therapy; Cancer immunotherapy; Chimeric antigen receptor; Cytotoxic release syndrome; Oncology
    DOI:  https://doi.org/10.1186/s43046-025-00262-6
  2. Recenti Prog Med. 2025 May;116(5): 272-284
    [The current role of CAR-T cell treatment in lymphoma therapy: focus on diffuse large cell lymphoma and mantle cell lymphoma.]
    Alessandro Broccoli, Pier Luigi Zinzani.
      The aim of this work is to provide the information needed to adequately apply chimeric antigen receptor T-cell (CAR-T) therapy in real clinical practice in outpatient, day hospital and ward settings, with a particular focus on patients with diffuse large cell lymphoma and mantle cell lymphoma, which currently represent the main area of use of anti-CD19 CAR-T treatment. The currently approved indications in both contexts are reviewed and the fundamental steps to follow in starting CAR-T cell therapy are described, as well as the data available in the literature regarding each previously presented indication.
    DOI:  https://doi.org/10.1701/4495.44947
  3. Gan To Kagaku Ryoho. 2025 Apr;52(4): 304-309
    [Enhancing CAR-T/CAR-NK Cells through by Cytokine Signaling].
    Yuki Kagoya.
      Chimeric antigen receptor(CAR)T-cell therapy has already been in the clinic due to its marked efficacy against several hematologic cancers. However, a significant number of patients relapse after a transient response, and the applicable diseases are still limited. Cytokine signaling is one of the most promising targets to enhance the therapeutic efficacy of CAR-T cells. At the same time, several cytokines are closely associated with toxicity, as exemplified by cytokine release syndrome. Here I will present representative findings on cytokines that have been shown to modulate CAR-T cell functions. I will also present our recent studies on how to simultaneously address efficacy and safety issues in CAR-T cell therapy. We will also briefly discuss CAR-NK cells, in which cytokines play an essential role.
  4. Arthritis Res Ther. 2025 May 10. 27(1): 102
    CAR-T cell therapy for juvenile-onset autoimmune diseases: a promising future?
    C3I consortium
      Chimeric antigen receptor (CAR) T-cell therapy targeting B cells has shown promising results, including drug-free remission, in adult-onset autoimmune diseases. Extending this therapeutic approach to the pediatric population, particularly for juvenile autoimmune diseases, presents an exciting opportunity. However, challenges specific to juvenile-onset autoimmune conditions, such as long-term adverse events, heightened disease activity, and the imperative to reduce steroid exposure, must be considered. While this strategy appears viable for these severe conditions, the limited data available for this population and the absence of evidence on cases with a high genetic component, such as monogenic lupus, represent significant challenges. Most monogenic lupus cases are associated with innate immune defects, and the involvement of B cells in these genetic anomalies remains poorly understood. In this review, we examine the potential indications, current knowledge, and limitations of CAR-T cell therapy in juvenile-onset autoimmune diseases, extending the discussion beyond early-onset lupus.
    Keywords:  Autoimmunity; B cells; CAR-T cells; CD19; Children; Juvenile dermatomyositis; Lupus; Monogenic lupus
    DOI:  https://doi.org/10.1186/s13075-025-03564-1
  5. Cancers (Basel). 2025 Apr 26. pii: 1454. [Epub ahead of print]17(9):
    Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies.
    Ugo Testa, Germana Castelli, Elvira Pelosi.
      The clinical use of T lymphocytes engineered with chimeric antigen receptors (CARs) has revolutionized the treatment of patients with refractory or relapsed hematological malignancies. CAR natural killer (CAR-NK) cells are NK cells engineered with CARs to specifically target cell antigens expressed on the membrane of tumor cells. CAR-NK cells could offer some advantages with respect to CAR-T cells, related to their specific and innate anti-tumor activity, availability as an "off the shelf" cellular therapy, reduced costs, and improved safety. Promising efficacy of CAR-Nk cell therapy was observed in clinical trials based on the treatment of some hematological malignancies. However, to date, the clinical experience of CAR-NK cell therapy has been preliminary, with the evaluation of only a limited number of patients. Furthermore, CAR-NK cell therapy has been limited by the short persistence of these cells and by the suboptimal cytotoxic activity of some CAR-NK preparations. Therefore, studies based on the enrollment of a number of patients is required to carefully assess and confirm the safety and the efficacy of CAR-NK cell therapy in hematological malignancies and to compare their efficacy with respect to allogeneic CAR-T cells.
    Keywords:  chimeric antigen receptor; hematological malignancies; immunotherapy; leukemia; lymphoma; multiple myeloma; natural killer
    DOI:  https://doi.org/10.3390/cancers17091454
  6. Front Immunol. 2025 ;16 1554541
    Prospects for γδ T cells and chimeric antigen receptor γδ T cells in cancer immunotherapy.
    Lu Wang, Jiaqi Li, Yaping Xuan, Jinrui Zhang, Xiao Wang, Wei Hu, Lei Xiu.
      γδ T cells, a type of specialized T cell, differ from alpha-beta T cells due to the presence of γ and δ chain surface T cell receptors. These receptors allow them to directly recognize and bind antigenic molecules without the requirement of attachment to MHC or APC antigen presentation. Given their intrinsic properties and functional versatility, γδ T cells are under intensive investigation as carriers for chimeric antigen receptor (CAR) in the context of cancer therapy. In this regard, γδ CAR-T cells have demonstrated great potential to overcome the limitations of antigen recognition with the help of dual antigen identification mechanisms. However, there are still technological challenges that need to be addressed. This discussion focuses on the research status and future development prospects of γδ T cells and γδ CAR-T cells, aiming to provide valuable insights for the follow-up research and practical application of γδ CAR-T cells.
    Keywords:  anti-tumor responses; cancer therapy; pro-tumor response; γδ CAR-T cells; γδ T cells
    DOI:  https://doi.org/10.3389/fimmu.2025.1554541
  7. Mediterr J Hematol Infect Dis. 2025 ;17(1): e2025039
    Toxicities Associated with CAR-T Cell Therapies.
    Ugo Testa, Germana Castelli, Elvira Pelosi, Eugenio Galli, Patrizia Chiusolo.
      Chimeric antigen receptor (CAR) T-cell therapy has improved the outcomes of patients with relapsed/refractory B-cell lymphomas, B-cell acute lymphoblastic leukemia, and multiple myeloma. However, CAR-T cell therapy is also associated with distinct toxicities that contribute to morbidity and mortality. A large number of studies now define the different toxicities associated with CAR-T cell therapy and have, in part, clarified their mechanisms. In particular, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two main acute toxicity events that occur after CAR-T cell infusion. Other CAR-T-related toxicities occur later after CAR-T cell infusion and include B-cell aplasia, hypogammaglobulinemia, infections, and cytopenias. Infections represent the main cause of non-relapse death observed in patients undergoing CAR-T cell therapy. Second primary malignancies are rare and are mainly represented by myeloid malignancies.
    Keywords:  Diagnosis; Heparin-binding protein; Infectious disease; Meta-analysis; Mortality; Organ failure; Prognosis; Sepsis; Systematic review
    DOI:  https://doi.org/10.4084/MJHID.2025.039
  8. Healthc Technol Lett. 2025 Jan-Dec;12(1):12(1): e70012
    An Analysis of Monitoring Solutions for CAR T Cell Production.
    Arber Shoshi, Yuchen Xia, Andrea Fieschi, Yannick Baumgarten, Andrea Gaißler, Thomas Ackermann, Peter Reimann, Bernhard Mitschang, Michael Weyrich, Thomas Bauernhansl, Robert Miehe.
      The chimeric antigen receptor T cell (CAR T) therapy has shown remarkable results in treating certain cancers. It involves genetically modifying a patient's T cells to recognize and attack cancer cells. Despite its potential, CAR T cell therapy is complex and costly and requires the integration of multiple technologies and specialized equipment. Further research is needed to achieve the maximum potential of CAR T cell therapies and to develop effective and efficient methods for their production. This paper presents an overview of current measurement methods used in the key steps of the production of CAR T cells. The study aims to assess the state of the art in monitoring solutions and identify their potential for online monitoring. The results of this paper contribute to the understanding of measurement methods in CAR T cell manufacturing and identify areas where on-line monitoring can be improved. Thus, this research facilitates progress toward the development of effective monitoring of CAR T cell therapies.
    Keywords:  CAR T cell therapy; advanced therapy medicinal product (ATMP); monitoring; on‐line measurement
    DOI:  https://doi.org/10.1049/htl2.70012
  9. Comput Biol Med. 2025 May 14. pii: S0010-4825(25)00683-3. [Epub ahead of print]192(Pt B): 110332
    The role of single cell transcriptomics for efficacy and toxicity profiling of chimeric antigen receptor (CAR) T cell therapies.
    Moritz Thomas, Ruben Brabenec, Lisa Gregor, David Andreu-Sanz, Emanuele Carlini, Philipp Jie Müller, Adrian Gottschlich, Donjete Simnica, Sebastian Kobold, Carsten Marr.
      CAR T cells are genetically modified T cells that target specific epitopes. CAR T cell therapy has proven effective in difficult-to-treat B cell cancers and is now expanding into hematology and solid tumors. To date, approved CAR therapies target only two specific epitopes on cancer cells. Identifying more suitable targets is challenged by the lack of truly cancer-specific structures and the potential for on-target off-tumor toxicity. We analyzed gene expression of potential targets in single-cell data from cancer and healthy tissues. Because safety and efficacy can ultimately only be defined clinically, we selected approved and investigational targets for which clinical trail data are available. We generated atlases using >300,000 cells from 48 patients with follicular lymphoma, multiple myeloma, and B-cell acute lymphoblastic leukemia, and integrated over 3 million cells from 35 healthy tissues, harmonizing datasets from over 300 donors. To contextualize findings, we compared target expression patterns with outcome data from clinical trials, linking target profiles to efficacy and toxicity, and ranked 15 investigational targets based on their similarity to approved ones. Target expression did not significantly correlate with reported clinical toxicities in patients undergoing therapy. This may be attributed to the intricate interplay of patient-specific variables, the limited amount of metadata, and the complexity underlying toxicity. Nevertheless, our study serves as a resource for retrospective and prospective target evaluation to improve the safety and efficacy of CAR therapies.
    Keywords:  Adoptive T cell therapy; CAR T cell therapy; Chimeric antigen receptor; Off-tumor toxicity; Single-cell sequencing; Target antigen
    DOI:  https://doi.org/10.1016/j.compbiomed.2025.110332
  10. Nanotechnology. 2025 May 16. 36(22):
    mRNA lipid nanoparticles in CAR-T therapy: a novel strategy to improve efficacy.
    Zengkai Zhao, Mingmei Li, Xiang Zheng, Pengli Gao, Chenlu Huang, Qingyu Yu, Limin Jin, Linhua Zhang, Dunwan Zhu, Fangzhou Li.
      Chimeric antigen receptor T cells (CAR-T) immunotherapy has achieved remarkable progress in the treatment of hematological malignancies. However, it encounters challenges including complex manufacturing processes, high cost, and safety issues. Lipid nanoparticle (LNP) technology, as an advanced gene delivery platform, offers significant advancements to CAR-T therapy through its high efficiency, low immunogenicity, and safety. LNP enablein vivoproduction of CAR-T cells, thereby improving delivery efficiency, reducing the risks of immunogenicity and insertional mutations, simplifying the production process and reducing costs. The scalability and rapid optimization ability of LNP position them as promising candidates for CAR-T cell production. LNP technology is expected to further promote the development of CAR-T immunotherapy and provide safer and more economical treatment options. Therefore, this paper aims to provide a comprehensive and systematic review of the application of LNP in CAR-T therapy. In this review, we initially outline the fundamental design, process, and current challenges of CAR-T therapy. Subsequently, we present the characteristics of LNP, their advantages as a gene delivery vectors, and how they improve the efficacy of CAR-T therapy. Finally, we summarize the current research landscape of LNP applications in CAR-T therapy. This includes enhancingin vitrotransfection of T cells, programming T cellsin situ, facilitating T-cell activation, alleviating the side effects of CAR-T therapy, and combining CAR-T therapy with other immunotherapies. These advancements will aid in the design of mRNA delivery systems based on LNP, thereby promoting the development of CAR-T therapy.
    Keywords:  CAR-T; immunotherapy; lipid nanoparticles; mRNA delivery
    DOI:  https://doi.org/10.1088/1361-6528/add482
  11. Neurooncol Adv. 2025 Jan-Dec;7(1):7(1): vdaf059
    Chimeric antigen receptor-macrophages: Emerging next-generation cell therapy for brain cancer.
    Myrthe J A Koppers, Matthijs Monnikhof, Jan Meeldijk, Thijs Koorman, Niels Bovenschen.
      Adoptive cell-based therapy utilizing chimeric antigen receptor (CAR)-T technology holds promise in the field of neuro-oncology. Significant progress has been made in enhancing both the efficacy and safety of CAR-T-cell therapies. However, challenges such as the multifaceted immunosuppressive impact of the tumor microenvironment and insufficient CAR-T-cell infiltration into brain tumor sites remain a major hurdles. Emerging novel approaches utilizing CAR-macrophages (CAR-MACs) show potent results for brain tumor immunotherapy. CAR-MACs localize to tumor sites more readily, increase immune cell infiltrates, and demonstrate high antitumor efficacy by effectively eliminating tumor cells through mechanisms such as phagocytosis or efferocytosis. This review discusses the current advancements in CAR-MAC cell therapies for brain cancer, followed by an overview of research on manufacturing CAR-MACs for clinical application. We further highlight the potential future applications of CAR-MACs in combinatory therapies in the treatment of brain tumors.
    Keywords:  CAR-macrophages; adoptive cell therapy; brain tumor; chimeric antigen receptor; tumor microenvironment
    DOI:  https://doi.org/10.1093/noajnl/vdaf059
  12. Adv Mater. 2025 May 09. e2412482
    Mechanostimulatory Platform for Improved CAR T Cell Immunotherapy.
    Abed Al-Kader Yassin, Carlos Ureña Martin, Guillaume Le Saux, Ashish Pandey, Sivan Tzadka, Esti Toledo, Jatin Jawhir Pandit, Tomer Sherf, Idan Nusbaum, Baisali Bhattachrya, Rajashri Banerji, Yariv Greenshpan, Muhammad Abu Abu Ahmad, Olga Radinsky, Menachem Sklartz, Roi Gazit, Moshe Elkabets, Sabah Ghassemi, Ofir Cohen, Mark Schvartzman, Angel Porgador.
      Chimeric Antigen Receptor T (CAR T) cell immunotherapy has revolutionized cancer treatment, yet it is hindered by rapid T-cell exhaustion caused by uncontrolled activation during CAR generation. Leveraging insights into T-cell mechanosensing, a novel mechanostimulatory platform is engineered for T-cell activation based on an antigen-carrying surface with controlled elasticity and nanotopography. The platform is designed to optimize and balance T-cell exhaustion, proliferation, and CAR expression. It enhances the differentiation of T cells into the central memory subset, which is crucial for the persistence of CAR T cell therapy's anticancer effects. The platform produces CAR T cells with higher antitumor efficacy, as validated through ex vivo experiments, and with higher in vivo persistence and ability to suppress tumor proliferation, as compared to CAR T cells generated by standard protocols. RNA-seq analysis confirmed an increased transcriptional signature of central memory T cells. Furthermore, this platform completely eliminates T-cell toxicity associated with the non-viral transfection process typically observed with standard activation methods. This platform presents a promising pathway for improving the efficiency and safety of CAR T cell therapy.
    Keywords:  CAR T cells; biomaterials; immunotherapy; mechanosensing
    DOI:  https://doi.org/10.1002/adma.202412482
  13. J Clin Med. 2025 Apr 25. pii: 2982. [Epub ahead of print]14(9):
    A Literature Review on the Impact of the Gut Microbiome on Cancer Treatment Efficacy, Disease Evolution and Toxicity: The Implications for Hematological Malignancies.
    Ioana Gabriela Dumitru, Samuel Bogdan Todor, Cristian Ichim, Claudiu Helgiu, Alina Helgiu.
      The gut microbiome plays a crucial role in modulating the efficacy and toxicity of cancer therapies, particularly in hematological malignancies. This review examines the dynamic interplay between gut microbiota and cancer treatments, such as chemotherapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT). Disruptions in the gut microbiome, known as dysbiosis, are associated with adverse effects like gastrointestinal toxicity, neutropenia and cardiotoxicity during chemotherapy. Conversely, the supplementation of probiotics has shown potential in mitigating these side effects by enhancing gut barrier function and regulating immune responses. In HSCT, a higher diversity of gut microbiota is linked to better patient outcomes, including reduced graft-versus-host disease (GVHD) and improved survival rates. The microbiome also influences the efficacy of immunotherapies, such as immune checkpoint inhibitors and CAR-T cell therapy, by modulating immune pathways. Research suggests that certain bacteria, including Bifidobacterium and Akkermansia muciniphila, enhance therapeutic responses by promoting immune activation. Given these findings, modulating the gut microbiome could represent a novel strategy for improving cancer treatment outcomes. The growing understanding of the microbiome's impact on cancer therapy underscores its potential as a target for personalized medicine and offers new opportunities to optimize treatment efficacy while minimizing toxic side effects.
    Keywords:  cancer therapy; dysbiosis; gut microbiome; hematological malignancies; immunotherapy; probiotics
    DOI:  https://doi.org/10.3390/jcm14092982
  14. Immun Inflamm Dis. 2025 May;13(5): e70189
    Clinical Progress in Mesenchymal Stem Cell Therapy: A Focus on Rheumatic Diseases.
    Helal F Hetta, Alaa Elsaghir, Victor Coll Sijercic, Abdulrahman K Ahmed, Sayed A Gad, Mahlet S Zeleke, Fawaz E Alanazi, Yasmin N Ramadan.
       BACKGROUND: Rheumatic diseases are chronic immune-mediated disorders affecting multiple organ systems and significantly impairing patients' quality of life. Current treatments primarily provide symptomatic relief without offering a cure. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their ability to differentiate into various cell types and their immunomodulatory, anti-inflammatory, and regenerative properties. This review aims to summarize the clinical progress of MSC therapy in rheumatic diseases, highlight key findings from preclinical and clinical studies, and discuss challenges and future directions.
    METHODOLOGY: A comprehensive review of preclinical and clinical studies on MSC therapy in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis, Sjögren's syndrome, Crohn's disease, fibromyalgia, systemic sclerosis, dermatomyositis, and polymyositis, was conducted. Emerging strategies to enhance MSC efficacy and overcome current limitations were also analyzed.
    RESULTS AND DISCUSSION: Evidence from preclinical and clinical studies suggests that MSC therapy can reduce inflammation, modulate immune responses, and promote tissue repair in various rheumatic diseases. Clinical trials have demonstrated potential benefits, including symptom relief and disease progression delay. However, challenges such as variability in treatment response, optimal cell source and dosing, long-term safety concerns, and regulatory hurdles remain significant barriers to clinical translation. Standardized protocols and further research are required to optimize MSC application.
    CONCLUSION: MSC therapy holds promise for managing rheumatic diseases, offering potential disease-modifying effects beyond conventional treatments. However, large-scale, well-controlled clinical trials are essential to establish efficacy, safety, and long-term therapeutic potential. Addressing current limitations through optimized treatment protocols and regulatory frameworks will be key to its successful integration into clinical practice.
    Keywords:  mesenchymal stem cells; osteoarthritis; rheumatic diseases; rheumatoid arthritis; systemic lupus erythematosus; systemic sclerosis
    DOI:  https://doi.org/10.1002/iid3.70189
  15. JAMA. 2025 May 12.
    The Microbiome and Cancer: A Translational Science Review.
    Estefania Fernandez, Jennifer A Wargo, Beth A Helmink.
       Importance: Growing evidence suggests that microbes located within the gastrointestinal tract and other anatomical locations influence the development and progression of diseases such as cancer.
    Observations: Clinical and preclinical evidence suggests that microbes in the gastrointestinal tract and other anatomical locations, such as the respiratory tract, may affect carcinogenesis, development of metastases, cancer treatment response, and cancer treatment-related adverse effects. Within tumors of patients with cancer, microbes may affect response to treatment, and therapies that reduce or eliminate these microbes may improve outcomes in patients with cancer. Modulating gastrointestinal tract (gut) microbes through fecal microbiota transplant and other strategies such as dietary intervention (eg, high-fiber diet intervention) has improved outcomes in small studies of patients treated with cancer immunotherapy. In contrast, disruption of the gut microbiota by receipt of broad-spectrum antibiotics prior to treatment with cancer immunotherapy has been associated with poorer overall survival and higher rates of adverse effects in patients treated with immune checkpoint blockade for solid tumors and also with chimeric antigen receptor T-cell therapy for hematologic malignancies.
    Conclusions and Relevance: Microbes in the gut and other locations in the body may influence the development and progression of cancer and may affect the response to adverse effects from cancer therapy. Future therapies targeting microbes in the gut and other locations in the body could potentially improve outcomes in patients with cancer.
    DOI:  https://doi.org/10.1001/jama.2025.2191
  16. Trends Immunol. 2025 May 13. pii: S1471-4906(25)00120-6. [Epub ahead of print]
    Using TCR-CAR dual signaling for precise cancer targeting.
    Mohammad Shahbazy, Isabelle Rose Leo, Pouya Faridi, Etienne Caron.
      Recently, Kondo et al. engineered the coexpression of a T cell receptor (TCR) and a chimeric antigen receptor (CAR) and developed an antagonism-enforced braking system where TCR signals both enhance and inhibit CAR activation. This work may enable rational design of CAR-T agents that limit toxicity to healthy tissue.
    Keywords:  CAR; T cell; TCR; immunotherapy; peptide
    DOI:  https://doi.org/10.1016/j.it.2025.04.007
  17. Med. 2025 May 06. pii: S2666-6340(25)00104-7. [Epub ahead of print] 100677
    Emerging trends in clinical allogeneic CAR cell therapy.
    Yan-Ruide Li, Yichen Zhu, Ying Fang, Zibai Lyu, Lili Yang.
      There has been significant progress in the clinical development of allogeneic off-the-shelf chimeric antigen receptor (CAR)-engineered cell therapies for the treatment of cancer and autoimmune diseases. Unlike autologous CAR cell therapies, allogeneic approaches overcome challenges such as high costs, labor-intensive manufacturing, and stringent patient selection. This makes allogeneic therapies a more universally applicable option for a diverse patient population. In this review, we examine recent clinical advancements in allogeneic CAR cell therapies, including CAR-T cell therapy derived from healthy donor peripheral blood mononuclear cells, as well as CAR-NK cell therapy from cord blood or induced pluripotent stem cells. We provide an overview of their genetic engineering strategies, clinical designs, and outcomes, highlighting their promising efficacy and safety. Additionally, we summarize key preclinical developments, address key challenges, and explore future directions to provide insights into emerging trends in the field.
    Keywords:  CAR-NK; CAR-NKT; CAR-T; GvHD; allogeneic CAR cell therapy; allorejection; autoimmune disease; cancer therapy; clinical trials; iPSC engineering; off-the-shelf
    DOI:  https://doi.org/10.1016/j.medj.2025.100677
  18. Mol Pharm. 2025 May 13.
    Advances in T Cell-Based Cancer Immunotherapy: From Fundamental Mechanisms to Clinical Prospects.
    Kaili Zhang, Yi Zhang, Pan Xiang, Yi Wang, Yifan Li, Shuze Jiang, Yuxuan Zhang, Min Chen, Weijun Su, Xiaoling Li, Shuai Li.
      T cells and their T cell receptors (TCRs) play crucial roles in the adaptive immune system's response against pathogens and tumors. However, immunosenescence, characterized by declining T cell function and quantity with age, significantly impairs antitumor immunity. Recent years have witnessed remarkable progress in T cell-based cancer treatments, driven by a deeper understanding of T cell biology and innovative screening technologies. This review comprehensively examines T cell maturation mechanisms, T cell-mediated antitumor responses, and the implications of thymic involution on T cell diversity and cancer prognosis. We discuss recent advances in adoptive T cell therapies, including tumor-infiltrating lymphocyte (TIL) therapy, engineered T cell receptor (TCR-T) therapy, and chimeric antigen receptor T cell (CAR-T) therapy. Notably, we highlight emerging DNA-encoded library technologies in mammalian cells for high-throughput screening of TCR-antigen interactions, which are revolutionizing the discovery of novel tumor antigens and optimization of TCR affinity. The review also explores strategies to overcome challenges in the solid tumor microenvironment and emerging approaches to enhance the efficacy of T cell therapy. As our understanding of T cell biology deepens and screening technologies advances, T cell-based immunotherapies show increasing promise for delivering durable clinical benefits to a broader patient population.
    Keywords:  Adoptive T cell therapy; Cancer immunoediting; DNA-encoded libraries; T cell-based immunotherapy; TCR engineering
    DOI:  https://doi.org/10.1021/acs.molpharmaceut.4c01502
  19. J Immunother Cancer. 2025 May 13. pii: e011278. [Epub ahead of print]13(5):
    Asia's emergence in cancer immunotherapy: challenges and opportunities.
    Yan Li, Joe Yeong, Bernard A Fox, Cheng Sun.
      Asia's role in cancer immunotherapy research is rapidly expanding, driven by cutting-edge facilities, innovative technologies, and collaborative efforts. This commentary examines the region's growing impact, highlighting key clinical trials, emerging research hubs, and unique challenges that we face. It discusses the need for standardization in cell and gene therapies, and more broadly all immunotherapies, addressing cost and accessibility issues. We examine the implications of genetic diversity in Asian populations as well as cultural and linguistic factors that affect clinical trials and patient care. The analysis extends to emerging opportunities in technological innovation and international collaboration, while addressing critical challenges in regulatory oversight, data transparency, and intellectual property protection. The success of the recent SITC-World Immunotherapy Council-Asia conference is showcased as a catalyst for future collaborations. By tackling these challenges and using innovations, Asian countries can significantly contribute to global advancements in cancer immunotherapy, potentially improving outcomes for patients worldwide.
    Keywords:  Immunotherapy
    DOI:  https://doi.org/10.1136/jitc-2024-011278
  20. J Immunother Cancer. 2025 May 13. pii: e011441. [Epub ahead of print]13(5):
    Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies.
    Christian Roy, Tomasz Sewastianik, Ileana Saenz, Gregory J Opiteck, Sean Stagg, Martin Maiers, Dirk Nagorsen.
      Understanding regional distribution of HLA frequencies is crucial for optimizing enrollment in HLA-restricted clinical trials and to promote trial diversity per the Food and Drug Administration's 2020 mandate. Using US HLA frequency data and census demographics we developed a method to create high-resolution HLA class 1 genotypic frequency maps. Analyzing HLA-A*11:01 and HLA-B*58:01 as alleles of interest, we found significant US regional variations. HLA-A*11:01, which presents KRAS neoantigen mutations targeted by TCR T-cell therapies, showed 10-15% genotypic frequency (national average 11.2%), with western US states 1.5 times higher than average and local variations within California (10-19%). These insights can be used to guide clinical trial site selection, for example, in National Cancer Institute (NCI) cancer center catchment areas. For HLA-B*58:01, which reacts pharmacogenetically with allopurinol and results in severe cutaneous adverse reactions, Mississippi had a high frequency among US states, which could be used to guide potential public safety campaigns. This method can identify regions with high HLA type representation, aiding efficient patient identification and enrollment for HLA-specific clinical trials and health-awareness efforts.
    Keywords:  Adoptive cell therapy - ACT; Genetic; Human leukocyte antigen - HLA; Major histocompatibility complex - MHC; T cell Receptor - TCR
    DOI:  https://doi.org/10.1136/jitc-2024-011441
  21. J Virol. 2025 May 14. e0045825
    Phage therapy: a promising approach for Staphylococcus aureus diabetic foot infections.
    Lucile Plumet, Chloé Magnan, Denis Costechareyre, Albert Sotto, Jean-Philippe Lavigne, Virginie Molle.
      Diabetic foot infections (DFIs), predominantly caused by Staphylococcus aureus, pose a significant healthcare challenge with severe consequences, including amputation. Phage therapy, which utilizes bacteriophages to specifically target bacterial pathogens, has emerged as a promising alternative to conventional antibiotic treatments. This review evaluates the efficacy of phage therapy as a complementary treatment for DFIs caused by S. aureus, synthesizing evidence from preclinical and clinical studies while addressing the limitations and challenges associated with current research. The analysis highlights promising results from diabetic animal models, demonstrating effective bacterial load reduction and improved wound healing. Clinical case reports and series further underline significant improvements in infection management and ulcer healing, with no major adverse effects reported. Ongoing clinical trials are also discussed, offering insights into the study parameters evaluating phage therapy potential efficacy and safety for S. aureus-related DFIs. While the collected data highlight the potential of phage therapy as a valuable complement to traditional antibiotic treatments, particularly in managing antibiotic-resistant infections, further research is essential to address existing limitations, including gaps in long-term efficacy data and challenges in standardization. With continued investigation, phage therapy holds significant potential to alleviate the healthcare burden of DFIs and improve patient outcomes.
    Keywords:  Staphylococcus aureus; animal models; bacteriophages; clinical cases; clinical trials; diabetic foot infections; phage therapy
    DOI:  https://doi.org/10.1128/jvi.00458-25
  22. Cell Rep Methods. 2025 May 07. pii: S2667-2375(25)00085-2. [Epub ahead of print] 101049
    Generation of T cell responses against broad KRAS hotspot neoantigens for cell therapy or TCR discovery.
    Brandon P Conn, Jared L Dietze, Christian J Yee, Margaret M Hallisey, Irais Ortiz-Caraveo, Marit M van Buuren, Richard B Gaynor, Kendra C Foley, Jaewon Choi, Vikram R Juneja.
      Adoptive cell therapy (ACT) with T cells targeting Kirsten rat sarcoma (KRAS) neoantigens can drive anti-tumor immunity but has so far been focused on a small fraction of known KRAS neoantigens. Here, we develop a single process starting from peripheral blood that can prime and expand T cell responses ex vivo to any KRAS neoantigen based on each individual's human leukocyte antigen (HLA) profile. We conducted the process in 20 healthy donors and generated T cell responses to 46 of 47 evaluated neoantigens. We identified and cloned more than 150 KRAS T cell receptors (TCRs), with the strongest TCRs having similar potency to clinically active benchmark TCRs. T cells generated through this process were able to slow tumor growth in vitro and in vivo. The approach could be used as the basis for the development of an ex vivo primed therapeutic or to discover a library of TCRs against a broad range of KRAS neoantigens.
    Keywords:  CP: biotechnology; CP: immunology; KRAS; T cell; TCR; adoptive cell transfer; cancer; immunotherapy; neoantigen
    DOI:  https://doi.org/10.1016/j.crmeth.2025.101049
  23. Adv Sci (Weinh). 2025 May 11. e2501095
    From Multi-Omics to Visualization and Beyond: Bridging Micro and Macro Insights in CAR-T Cell Therapy.
    Yuting Gong, Peng Fei, Yicheng Zhang, Yang Xu, Jia Wei.
      Chimeric antigen receptor T (CAR-T) cell therapies, a cornerstone of immunotherapy, have demonstrated remarkable efficacy in treating hematological malignancies and have more recently expanded into applications for solid tumors and autoimmune diseases. Emerging multidimensional profiling technologies offer promising solutions for enhancing CAR-T efficacy, overcoming resistance, and facilitating the development of novel CAR-T constructs. The integration of genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics enables a comprehensive understanding of the intrinsic mechanisms underlying CAR-T therapy, while single-cell and spatial omics significantly improve data resolution and analytical depth. Coupled with advances in biomedical engineering, visualization technologies form the foundation for omics data generation by bridging microscopic and macroscopic scales and enabling dynamic, 3D in vivo monitoring of CAR-T behavior. Artificial intelligence (AI) further supports this framework by enabling the analysis of complex, high-dimensional datasets. This review highlights recent advances in the integration of multidimensional omics within CAR-T therapy and explores cutting-edge developments in visualization technologies and AI applications. The full convergence of multi-omics, visualization tools, and AI is poised to deliver transformative insights into the mechanisms governing CAR-T cell therapy.
    Keywords:  CAR‐T therapy; artificial intelligence; multi‐omics; single cell sequencing; spatial omics; tumor microenvironment; visualization
    DOI:  https://doi.org/10.1002/advs.202501095
  24. Cancer Control. 2025 Jan-Dec;32:32 10732748251341520
    Socioeconomic Status and Breast Cancer Treatment in the United States: Results From a Systematic Literature Review.
    Sreelatha Akkala, Mohammed Zuber, Julie Alaere Atta, Nompumelelo O Mzizi, Jyothi Akkula.
      BackgroundIn 2024, breast cancer is the second most common cancer globally, affecting 2.3 million women. In the United States (US), 310 720 new female breast cancer cases were estimated in 2024. Existing research has identified substantial disparities in breast cancer treatment and survival based on socioeconomic status (SES). This systematic review examines the association between the key SES indicators income, education, and occupation on breast cancer outcomes among the US breast cancer patients.MethodsAn electronic search was conducted using Medline®, Embase®, and Web of Science, from inception to December 2023. Observational studies examining the influence of SES indicators on breast cancer outcomes, including treatment receipt, adherence, and survival, were included. Data were summarized qualitatively due to heterogeneity in SES measures and outcome definitions.ResultsOf 2600 studies retrieved from the searches, 23 studies met the inclusion criteria (19 cohort, 4 cross-sectional). Women with lower SES were less likely to receive or experience delay in receiving the recommended treatment than women with higher SES. In addition, women with low household income (<$25,000) were more likely to report discontinuations in therapy as compared to women with an income of $50,000 or more. Education level influenced treatment adherence and timely care, with higher educational attainment linked to improved survival rates. Occupational status impacted treatment continuity, with low-wage jobs and inflexible work schedules contributing to delays and discontinuation of care.ConclusionSES significantly influences breast cancer care and survival, with lower SES associated with delayed treatment, poorer adherence, and worse outcomes. Healthcare interventions and policies focusing on equitable access to quality care tailored to all women, regardless of their socioeconomic background, may improve breast cancer outcomes for the patients with various demographic characteristics in the US.
    Keywords:  access to care; breast cancer; breast cancer treatment disparities; health care disparities; social determinants of health; socioeconomic status; treatment delay
    DOI:  https://doi.org/10.1177/10732748251341520
  25. Front Immunol. 2025 ;16 1499663
    Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families.
    Ran Liu, Xinyan Jiang, Ruijuan Dong, Yuting Zhang, Cong Gai, Peng Wei.
      Host immune responses to antigens are tightly regulated through the activation and inhibition of synergistic signaling networks that maintain homeostasis. Stimulatory checkpoint molecules initiate attacks on infected or tumor cells, while inhibitory molecules halt the immune response to prevent overreaction and self-injury. Multiple immune checkpoint proteins are grouped into families based on common structural domains or origins, yet the variability within and between these families remains largely unexplored. In this review, we discuss the current understanding of the mechanisms underlying the co-suppressive functions of CTLA-4, PD-1, and other prominent immune checkpoint pathways. Additionally, we examine the IgSF, PVR, TIM, SIRP, and TNF families, including key members such as TIGIT, LAG-3, VISTA, TIM-3, SIRPα, and OX40. We also highlight the unique dual role of VISTA and SIRPα in modulating immune responses under specific conditions, and explore potential immunotherapeutic pathways tailored to the distinct characteristics of different immune checkpoint proteins. These insights into the unique advantages of checkpoint proteins provide new directions for drug discovery, emphasizing that emerging immune checkpoint molecules could serve as targets for novel therapies in cancer, autoimmune diseases, infectious diseases, and transplant rejection.
    Keywords:  co-suppressive pathways; immune checkpoint proteins; immunotherapy; protein families; tumor microenvironment specificity
    DOI:  https://doi.org/10.3389/fimmu.2025.1499663
  26. Brief Bioinform. 2025 May 01. pii: bbaf207. [Epub ahead of print]26(3):
    An overview of computational methods in single-cell transcriptomic cell type annotation.
    Tianhao Li, Zixuan Wang, Yuhang Liu, Sihan He, Quan Zou, Yongqing Zhang.
      The rapid accumulation of single-cell RNA sequencing data has provided unprecedented computational resources for cell type annotation, significantly advancing our understanding of cellular heterogeneity. Leveraging gene expression profiles derived from transcriptomic data, researchers can accurately infer cell types, sparking the development of numerous innovative annotation methods. These methods utilize a range of strategies, including marker genes, correlation-based matching, and supervised learning, to classify cell types. In this review, we systematically examine these annotation approaches based on transcriptomics-specific gene expression profiles and provide a comprehensive comparison and categorization of these methods. Furthermore, we focus on the main challenges in the annotation process, especially the long-tail distribution problem arising from data imbalance in rare cell types. We discuss the potential of deep learning techniques to address these issues and enhance model capability in recognizing novel cell types within an open-world framework.
    Keywords:  cell type annotation; continual learning; dynamic clustering; long-tail distribution; open-world cell recognition; scRNA-seq
    DOI:  https://doi.org/10.1093/bib/bbaf207
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