bims-carter Biomed News
on CAR-T Therapies
Issue of 2025–07–06
sixteen papers selected by
Luca Bolliger, lxBio



  1. Crit Rev Oncol Hematol. 2025 Jul 01. pii: S1040-8428(25)00212-4. [Epub ahead of print] 104824
      Chimeric antigen receptor T (CAR-T) cell therapy represents a significant advancement in tumor immunotherapy, demonstrating notable efficacy in the treatment of hematological malignancies. Nevertheless, single-target CAR-T therapy encounters several challenges, including antigen escape, on-target off-tumor toxicity, and tumor heterogeneity. To address these limitations, dual-target CAR-T cell therapy has been developed. By recognizing two tumor antigens, dual-target CAR-T therapy broadens the antigen recognition spectrum of CAR-T cells and substantially mitigates the risk of antigen escape. Additionally, the incorporation of logic gate control design enhances its precision and minimizes on-target off-tumor toxicity. This review provides a comprehensive analysis of various dual-target CAR-T cell types, including sequential CAR-T cells, dual-signal CARs, tandem CARs, AND-gate CARs, and inhibitory CARs, with a focus on their applications and therapeutic efficacy in hematological malignancies. Furthermore, this review provides an in-depth examination of the unique advantages, current research progress, and challenges associated with dual-target CAR-T cell therapy.
    Keywords:  advantages; challenges; coping strategies; dual-target CAR-T cells; hematological malignancies
    DOI:  https://doi.org/10.1016/j.critrevonc.2025.104824
  2. J Rheum Dis. 2025 Jul 01. 32(3): 154-165
      Chimeric Antigen Receptor (CAR) T-cell therapy, revolutionary in treating hematological malignancies, is emerging as a promising approach for systemic autoimmune rheumatic diseases (SARDs). This review examines the potential of CAR T-cell therapy in treating conditions such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIMs). The evolution of CAR T cells technology, from first to fifth generation, has enhanced its efficacy and persistence. Early clinical studies in SARDs have shown encouraging results, with some patients achieving drug-free remission. CD19-targeted CAR T cells have demonstrated significant B-cell depletion and clinical improvement in patients with SLE, SSc, and IIMs. Despite promising outcomes, challenges remain, including cytokine release syndrome and the need for careful patient selection. Future directions include exploring dual-targeting CARs, chimeric autoantibody receptors (CAARs), and alternative cell sources like γδ T cells, regulatory T cells, natural killer cells. The integration of CAR-based cell therapy into treatment paradigms of patients with SARDs requires further research to optimize efficacy, mitigate side effects, and identify suitable target biomarkers. While hurdles exist CAR-based cell therapy holds the potential to revolutionize management of patients with SARDs, offering hope for long-term, drug-free remission in these complex autoimmune conditions.
    Keywords:  Autoimmune diseases; Chimeric Antigen Receptor T-cell therapy; Idiopathic inflammatory myopathy; Systemic lupus erythematosus; Systemic sclerosis
    DOI:  https://doi.org/10.4078/jrd.2024.0122
  3. Nat Rev Rheumatol. 2025 Jul 02.
    Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group*
      Initial success with B cell-targeted chimeric antigen receptor (CAR) T cells for the treatment of systemic lupus erythematosus and other rheumatic diseases has generated enthusiasm for the broad application of this technology outside of the field of oncology. Paediatric patients with severe rheumatic diseases require lifelong therapy with a substantial toxicity burden and a high cost of care. Paradigm-shifting treatments, including CAR T cells, are desperately needed. Although CAR T cell therapy shows promise for paediatric rheumatic diseases, there are unique aspects of care compared with adults, which require careful consideration and expertise. In response, we established the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group, comprising international experts in the fields of paediatric rheumatology, oncology and cellular therapy, immunology and nephrology, to address the challenges of introducing cell therapies to patients with paediatric-onset autoimmune diseases. Given the possible benefits, we advocate for the study of CAR T cells in paediatric patients with rheumatic diseases who carry a lifelong risk of morbidity and mortality from chronic illness and medication toxicity. As this patient population is relatively small, consensus around definitions of success, robust study of predictors of response and uniform assessment and reporting of toxicities are critical to advancing the field.
    DOI:  https://doi.org/10.1038/s41584-025-01272-3
  4. Sci Adv. 2025 Jul 04. 11(27): eadv4937
      Chimeric antigen receptor (CAR) T cell therapy has shown extraordinary results in treating hematological cancer but faces challenges like antigen loss, toxicity, and complex manufacturing. Universal and modular CAR constructs offer improved flexibility, safety, and cost-effectiveness over conventional CAR constructs. We present a CAR-fragment antibody binder (Fab) platform on the basis of an engineered protein G variant (GA1) and Fab scaffolds. Expression of GA1CAR on human CD8+ T cells leads to antigen recognition and T cell effector function that can be modulated according to the affinity of the CAR for the Fab and of the Fab for the target. GA1CAR T cells can recognize multiple Fab-antigen pairs on breast and ovarian cancer cell lines. Adoptively transferred GA1CAR T cells control tumors in breast cancer xenograft models, and their targeting can be quickly redirected using different Fabs. This versatile "plug-and-play" CAR T platform has potential for application in personalized therapy, preventing antigen loss variant escape, decreasing toxicity, and increasing access.
    DOI:  https://doi.org/10.1126/sciadv.adv4937
  5. Cell Stem Cell. 2025 Jul 03. pii: S1934-5909(25)00230-9. [Epub ahead of print]32(7): 1031-1033
      Toxicity and immune evasion have hindered the success of CAR T cells in HER2-positive solid tumors. In this issue of Cell Stem Cell, Hosking et al. present an iPSC-derived CAR T cell product engineered for tumor-selective targeting, resistance to the immunosuppressive tumor microenvironment, enhanced persistence and trafficking, and mitigation of antigen escape.
    DOI:  https://doi.org/10.1016/j.stem.2025.06.008
  6. Emerg Med Clin North Am. 2025 Aug;pii: S0733-8627(25)00024-0. [Epub ahead of print]43(3): 503-515
      Chimeric antigen receptor T-cell therapy is a modern approach in our treatment of cancer. However, it is not without potential side effects. While cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are some of the more well-known toxicities, other potential complications include B- and T-cell aplasia/hypogammoglobulinemia, opportunistic infections, various coagulopathies, graft versus host syndrome, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, and on-target off-tumor toxicities. Having a high index of suspicion is important when encountering patients with these conditions.
    Keywords:  Aplasia; CAR T; CRES; CRS; Chimeric antigen receptor toxicity; Coagulopathy; Cytokine release syndrome; Cytopenia; GVHD; Graft versus host; Hemophagocytic lymphohistiocytosis; Hypogammaglobulinemia; ICANS; Immune effector cell; Neurotoxicity; Toxicity
    DOI:  https://doi.org/10.1016/j.emc.2025.04.004
  7. Mater Today Bio. 2025 Aug;33 101965
      Natural killer (NK) cells are proving a powerful platform in cancer immunotherapy due to their innate cytotoxicity and ability to recognize tumor cells independently of antigen presentation. In preclinical and clinical studies, engineered NK cells expressing chimeric antigen receptors (CARs) have demonstrated strong antitumor efficacy, showcasing the potential of genetic reprogramming to enhance specificity and activation. In parallel, biomaterial-assisted surface engineering has gained momentum as a complementary strategy, offering a genome-independent and modular means of customizing NK cell functionality. Recent advances in covalent conjugation, metabolic glycoengineering, bio-orthogonal click chemistry, and hydrophobic insertion using biomaterials have facilitated the precise presentation of targeting ligands and immunomodulatory molecules directly onto the NK cell membrane. These strategies support programmable cell-tumor interactions, while maintaining the native cytotoxicity of NK cells. Although several challenges remain, including in vivo persistence and control of effector responses, surface engineering approaches offer practical advantages in flexibility, reversibility, and manufacturing. This review highlights key advances in NK cell-based cancer immunotherapy, with particular focus on: (1) the therapeutic potential and clinical application of native NK cells, (2) the development of CAR-NK cell platforms, and (3) emerging biomaterial-assisted surface engineering strategies to enhance immune synapse. Together, these developments expand the toolkit for NK cell-based therapies and suggest that material-guided engineering may play a valuable role alongside genetic strategies in shaping the next generation of cancer immunotherapy.
    Keywords:  Cancer immunotherapy; Chimeric antigen receptor; Immunological synapse; Lipid-based polymeric biomaterial; Natural killer cell; Surface engineering
    DOI:  https://doi.org/10.1016/j.mtbio.2025.101965
  8. Clin Rheumatol. 2025 Jul 04.
      Systemic sclerosis (SSc) is a complex disease with extensive fibrosis, microvasculopathy, and autoantibodies. Activation of the adaptive immune system involving T cells, B cells, and macrophages along with microvasculopathy is considered early events in disease pathogenesis. Today, immunosuppressives, including anti-B cell biologics, form the foundation of SSc treatment; however, significant therapeutic needs remain unmet. Autologous chimeric antigen receptor (CAR)-T cells, targeting B cell CD19 and inducing deep depletion of B cells, were tested in a few patients with SSc, leading to improvement of skin score, arthritis, digital ulcers, and inflammatory changes in heart and lungs. However, regression of lung fibrosis remains a major therapeutic challenge. In addition, autologous CAR-T cells are a personalized treatment that requires a specialized setting, is not readily available, is costly, and is associated with serious adverse effects, including cytokine release syndrome, neurotoxicity, and increased risk of infection. New developments in CAR T cell technology, including off-the-shelf allogeneic CAR T cells, bispecific CAR-T cells, and CAR NK cells, are being tested in patients with progressive refractory SSc. Key Points • There is unmet therapeutic need for systemic sclerosis(SSc). • Autologous CAR-T cells targeting CD19 showed efficacy in SSc, but are a personalized, expensive and not readily available treatment. • Off-the-shelf allogeneic CAR-T cells and CAR-NK cells are being evaluated in SSc.
    Keywords:  Adverse effects; B cells; Bispecific monoclonal antibodies; T cells
    DOI:  https://doi.org/10.1007/s10067-025-07554-1
  9. Immunotargets Ther. 2025 ;14 631-654
      Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with high rates of recurrence even after curative-intent treatments such as hepatectomy and liver transplantation (LT). In recent years, immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape for HCC, demonstrating significant efficacy among advanced-stage tumors through combination regimens, such as anti-programmed cell death ligand-1 (PD-L1)/PD-1 inhibitors with anti-vascular endothelial growth factor agents. Recent advances have highlighted the potential of ICIs as adjuvant therapy to improve recurrence-free survival among high-risk patients post-resection. However, challenges such as low immunogenicity, the immunosuppressive tumor microenvironment, and immune resistance remain substantial barriers to the broader success of ICIs. In the context of LT, the use of ICIs is further complicated by the concurrent need for immunosuppressive agents, which can exacerbate the risk of recurrence. Emerging strategies focusing on the optimization of the timing of ICI therapy and the utilization of novel biomarkers are being explored to mitigate graft rejection while maintaining antitumor efficacy. Additionally, immune-cell-based therapies based on chimeric antigen receptor-T and natural killer (NK) cells, adoptive cell transfer, and liver-resident NK cell approaches are also being investigated for their potential to reduce recurrence and improve survival outcomes. This review focuses on the current landscape of adjuvant immunotherapy and immune-cell therapy in the postoperative management of HCC, highlighting ongoing clinical trials, therapeutic potential, and associated risks. With continued advancements in immunotherapeutic strategies and personalized approaches, these therapies hold the promise of transforming outcomes for patients undergoing curative resection or LT.
    Keywords:  adjuvant immunotherapy; hepatectomy; hepatocellular carcinoma; immune checkpoint inhibitors; immune-cell therapy; liver transplantation
    DOI:  https://doi.org/10.2147/ITT.S528709
  10. Int J Nanomedicine. 2025 ;20 8085-8099
      Delivery of nano-therapeutics through the nasal route offers a promising approach for several applications, including intranasal conditions, pulmonary delivery, brain targeting, and vaccination. Despite its potential, this method faces significant challenges, including overcoming the mucosal barrier, ensuring consistent absorption, controlling the deposition area, and managing immunogenic responses. This review provides a comprehensive overview of the current state of nasally delivered lipid nanoparticles (LNPs) for gene medicine, focusing on the specific barriers encountered in this delivery route and strategies to overcome them. We examine how formulation composition affects stability during aerosolization, analyze the impact of particle characteristics on mucociliary clearance, and evaluate interactions with the lung surfactant layer. The review also compares delivery devices including metered-dose inhalers, dry powder inhalers, and nebulizers, highlighting how device selection influences LNP integrity and deposition patterns. Furthermore, we explore potential safety considerations with intranasal LNPs and propose approaches to mitigate adverse effects. By addressing these challenges with evidence-based strategies, this review aims to advance the development and clinical application of intranasal and pulmonary LNP delivery systems for gene-based therapeutics and vaccines.
    Keywords:  LNPs; gene medicine; intranasal delivery; lipid nanoparticles
    DOI:  https://doi.org/10.2147/IJN.S517385
  11. Recent Pat Nanotechnol. 2025 Jun 27.
      This editorial article explores the emerging field of AI-based nanotechnology, emphasizing its potential to transform various industries. It details how AI's data-processing capabilities synergies with nanotechnology's manipulation at the nanoscale. Within the medical field, for instance, this synergy has the potential to facilitate precise cancer treatment and early disease detection. The field of manufacturing also stands to benefit from the optimization of nanomaterial production. The article goes on to discuss the potential of AI-based 3D printing and MEMS applications, highlighting the enhancement of capabilities that these technologies offer. Notwithstanding the challenges, including data misuse and integration issues, that are ethically and technically complex, the potential benefits justify the risks. The article calls for collaboration among scientists, policymakers, and industry to foster responsible research and development and to unlock the full potential of this transformative combination, offering solutions to global challenges.
    Keywords:  3d printing; AI-based nanotechnology; industry collaboration.; manufacturing; medical applications; mems; ethical and technical challenges; physics-informed AI technology
    DOI:  https://doi.org/10.2174/0118722105384013250623094407
  12. Ann Pharm Fr. 2025 Jun 27. pii: S0003-4509(25)00106-3. [Epub ahead of print]
      From 2021-2024, the U.S. Food and Drug Administration (FDA) approved novel drugs, advancing treatments in neurology, oncology, infectious diseases and rare disorders. This review analyzes approval trends, highlighting the targeted diseases and biologics, the rise of expedited pathways and focus on unmet medical needs and examines key therapeutic areas the approval trends of different categories. The analysis draws on data from the FDA's Center for Drug Evaluation and Research (CDER) to provide insights into novel drug indication, regulatory innovations and their implications to healthcare. The review analyzes trends in drug approvals.
    Keywords:  U.S. FDA; approvals trends; approved drugs; regulatory trends; therapeutic areas
    DOI:  https://doi.org/10.1016/j.pharma.2025.06.004
  13. Biomark Res. 2025 Jul 01. 13(1): 92
      Multiple myeloma is a hematologic malignancy characterized by complex genetic and microenvironmental factors that drive disease progression and resistance to treatment. Despite advancements in therapies targeting established antigens, such as BCMA, CD38, SLAMF7, and GPRC5D, specific challenges persist, including antigen escape, treatment resistance, and off-tumor toxicity, highlighting the urgent need for novel therapeutic modalities. Recent advances in surface proteomics and integrative omics technologies have enabled the discovery of new surface antigens with the potential to address the challenges. By targeting antigens with higher tumor specificity and lower expression in healthy tissues, emerging immunotargets offer new avenues to minimize off-tumor toxicity and reduce the risk of relapse due to antigen loss or immune evasion. This review provides an overview of emerging immunotargets, summarizing their biological functions, roles in disease pathogenesis and immune evasion, and potential for therapeutic interventions. We focused on fifteen emerging targets currently in early clinical development or the preclinical phase, highlighting LILRB4, SEMA4A, ITGB7, CCR1, and CD70 as the most promising. These immunotargets demonstrate significant potential for next-generation immunotherapies, including antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies. Preclinical or early clinical studies show favorable safety profiles, high tumor specificity, and mechanisms to overcome immune resistance, collectively suggesting the potential for improved patient outcomes and reduced adverse effects. By presenting a comprehensive summary of these advances, this review underscores the translational potential of emerging immunotargets and provides insights to guide the development of innovative therapeutic approaches to improve outcomes for multiple myeloma patients.
    Keywords:  Aberrant plasma cells; Biomarker discovery; Hematooncology; Immunotarget; Immunotherapy; Multiple myeloma; Surface proteome; Surfaceomics
    DOI:  https://doi.org/10.1186/s40364-025-00799-7
  14. Front Immunol. 2025 ;16 1613494
      Exosomes are nanoscale, double-membraned vesicles released by a variety of living cells. A wide variety of cargoes, including proteins, DNA and RNA, are transported by exosomes to target cells, thereby transmitting biological signals. In addition to being an essential component of the exosomal cargo, exosomal proteins are a reflection of the physiological state of the originating cell, and play an essential part in intercellular communication in numerous diseases, including cancer. The present review provides a summary of the novel uses of exosomal proteins in cancer diagnosis and prognosis, and highlights the distinct qualities that exosomal proteins possess, when compared with typical serological measurements.
    Keywords:  biomarkers; cancer diagnosis; exosomal proteins; exosomes; treatment
    DOI:  https://doi.org/10.3389/fimmu.2025.1613494
  15. Biogerontology. 2025 Jul 01. 26(4): 138
      The field of longevity interventions has witnessed rapid expansion, driven by scientific advancements alongside growing industry and consumer interest. However, no longevity intervention has yet been proven effective or ready for widespread clinical adoption. A substantial gap persists between public expectations and the current scientific realities. This article explores four key themes: (1) consumer priorities regarding longevity interventions, (2) the type and depth of scientific information they value, (3) psychological, financial, and practical barriers limiting adoption, and (4) potential strategies to overcome these challenges. Despite increasing enthusiasm, clinical translation of longevity research is constrained by the lack of validated interventions, regulatory frameworks, and standardized biomarkers. By distinguishing between scientifically supported and unproven approaches, this article proposes a roadmap outlining the critical milestones necessary to advance longevity interventions from research to clinical readiness. The goal is to realign public understanding with the current state of longevity science and guide future efforts toward safe and effective translation.
    Keywords:  Healthspan; Longevity intervention; Public perception; Roadmap; Translational science
    DOI:  https://doi.org/10.1007/s10522-025-10278-z
  16. Eur J Med Res. 2025 Jul 01. 30(1): 524
      Vascular diseases (VD), such as cardiovascular diseases, cerebrovascular diseases, and diabetic diseases, originate from numerous pathophysiological changes and remain a serious public health concern. Extracellular vesicles (EVs) produced by cells contribute to regulating VD either dangerously or beneficially. The term EVs refers to the heterogeneous population of vesicles, such as exosomes and microvesicles that participate in cell communication during VD. EVs from different cells, especially those of stem cells, show great promise in the improvement of various VD. They can repair cellular damage, enhance and recover cell function, multiply cells, and prevent cell death and inflammation in specific tissues/cells. EVs have the potential to enhance conditions like cardiovascular disease, cerebrovascular disorders, and complications related to diabetes. Furthermore, an increasing amount of evidence indicates that EVs can be altered/loaded to create a drug delivery system for transporting therapeutic agents to cells, improving different VD. Different methods are used to engineer EVs to improve the efficacy of natural EVs. Despite the potential clinical application of EVs, this field facese many problems that need to be addressed. These limitations and challenges have unmasked the unexpected complexity of EVs regulatory mechanisms, and inspiring advances have been achieved.
    Keywords:  Cardiovascular disease; Cerebrovascular diseases; Exosomes; Extracellular vesicle; MiRNA
    DOI:  https://doi.org/10.1186/s40001-025-02822-x