bims-carter Biomed News
on CAR-T Therapies
Issue of 2025–09–07
28 papers selected by
Luca Bolliger, lxBio



  1. Front Immunol. 2025 ;16 1613878
      Although current treatments for autoimmune diseases can effectively control symptoms, they rarely lead to cures and often require lifelong use, accompanied by considerable adverse effects. This emphasizes the urgent need for more targeted therapies that offer long-term efficacy and curative potential. Chimeric antigen receptor (CAR) T-cell therapy presents a promising option by specifically targeting and eliminating autoreactive B cells, with the potential to reset the patient's immune system and promote long-term immune balance. Originally developed for treating hematologic malignancies, where it has achieved remarkable success, recent studies have demonstrated substantial promise of CAR T-cell therapy, such as systemic lupus erythematosus (SLE) and myasthenia gravis. This article provides an overview of the current progress in CAR T-cell therapy for autoimmune diseases, focusing on five key approaches: CD19-targeted CAR T cells, CAR T cells targeting long-lived plasma cells, CAR T cells targeting specific autoantibodies, organ-specific CAR regulatory T cells (Treg cells), and mRNA-engineered CAR T cells. Additionally, this article discusses strategies for optimizing CAR T-cell therapy, including "off-the-shelf" allogeneic CAR T-cell therapy, combined CAR T-cell therapy, establishing timely consensus guidelines for their application in autoimmune diseases, and risk stratification strategies aimed at enhancing the personalization of treatments and minimizing adverse effects. While current research results are promising, further large-scale clinical trials and long-term follow-up are essential to thoroughly evaluate the safety and efficacy of CAR T-cell therapy in autoimmune diseases.
    Keywords:  CAR T-cell therapy; Treg cell; autoimmune disease; autoreactive B cell targeting; personalized risk stratification
    DOI:  https://doi.org/10.3389/fimmu.2025.1613878
  2. Front Immunol. 2025 ;16 1655095
      Chimeric Antigen Receptor (CAR)-engineered cell therapies excel against hematologic malignancies, however, their efficacy in solid tumors is hampered by toxicity, poor tumor infiltration, immunosuppressive microenvironments, limited persistence, and expansion difficulties. Recently, exosomes derived from CAR-immune cells (CAR-Exosomes) have emerged rapidly as an innovative therapeutic platform. CAR-Exosomes, utilizing nanoscale communication pathways, inherit their parental cells' tumor-targeting capabilities while offering distinct advantage. These advantages encompass low immunogenicity, enhanced tissue penetration, and versatile drug-loading capacity, presenting a promising approach to circumvent the limitations of traditional cell therapies. This review systematically summarizes the core challenges for CAR-T, CAR-NK, and CAR-M cell therapies and emphasizes recent advancements in CAR-Exosomes, including their molecular characteristics, targeted recognition mechanisms, tumor-killing pathways, biosafety, and engineering strategies. Furthermore, it also discusses the key challenges and strategies in the clinical translation of CAR-Exosomes. In conclusion, integrating nanomedicine with cell therapy, CAR-Exosomes hold significant promise as a next-generation platform aiming for high efficacy, safety, and broad clinical applicability in cancer immunotherapy.
    Keywords:  CAR; cancer; cell-free; exosomes; immunotherapy
    DOI:  https://doi.org/10.3389/fimmu.2025.1655095
  3. Front Immunol. 2025 ;16 1600403
      Central nervous system (CNS) tumors are the second most common type of cancer in children and remain the leading cause of mortality in pediatric oncology. For patients with high-risk CNS tumors, standard treatments often prove ineffective, with survival rates being less than 10%. Hence, there is an urgent need to develop alternative treatment strategies for this patient population. Globally, numerous clinical trials are actively investigating a range of novel therapeutic approaches, from pharmacological and immunological therapies to physical modalities targeting the tumor. Among these emerging therapies, CAR T cell therapy has shown great promise, with the first objective clinical responses already reported. This review aims to evaluate the current landscape of CAR T cell therapy for pediatric CNS tumors, focusing on clinical efficacy, toxicity profiles of systemic and locoregional delivery, antigen heterogeneity, and key challenges in clinical implementation. We provide a comprehensive analysis of reported clinical trials, including not only CAR T cell studies but also investigations involving tumor-infiltrating lymphocytes (TILs), NK and lymphokine-activated killer (LAK) cells, offering a broader perspective on immunotherapeutic approaches for CNS malignancies.
    Keywords:  CAR T; CAR T solid tumors; CNS tumors; DIPG; DMG; brain cancer; glioblastoma; glioma
    DOI:  https://doi.org/10.3389/fimmu.2025.1600403
  4. J Hematol Oncol. 2025 Aug 29. 18(1): 82
      While chimeric antigen receptor (CAR) T cell therapy is highly effective for hematological malignancies, its widespread use is limited by complex, patient-specific manufacturing. Universal CAR-T (UCAR-T) cells, derived from allogeneic donors, offer a potential "off-the-shelf" solution. However, their clinical translation hinges on overcoming two key immunological barriers: graft-versus-host disease (GvHD) and host-versus-graft rejection (HvGR), which compromise safety and therapeutic persistence. This review summarizes recent advances in UCAR-T cell engineering and clinical strategies designed to improve both safety and efficacy. We discuss gene-editing technologies-such as CRISPR/Cas9 and base editors-used to prevent GvHD by ablating the T cell receptor (TCR) and to evade HvGR by disrupting human leukocyte antigen (HLA) expression. We also explore the development of UCAR-T products from alternative cell sources with low intrinsic alloreactivity, such as γδ T cells. Furthermore, we detail multifaceted approaches to augment UCAR-T cell function and persistence, from the perspectives of enhancing intrinsic functions, reshaping the tumor microenvironment (TME) and overcoming tumor heterogeneity. Finally, we analyze recent clinical trial outcomes, which show promising efficacy in hematological malignancies but highlight ongoing challenges in solid tumors. The continued integration of sophisticated cellular engineering with innovative clinical strategies-such as enhanced lymphodepletion, combination therapies, and alternative administration routes-will be essential to realize the full potential of UCAR-T as a widely accessible and potent cell therapy.
    Keywords:  Clinical strategy; Clinical trend; Efficacy; GvHD; HvGR; Solid tumor; UCAR-T cells
    DOI:  https://doi.org/10.1186/s13045-025-01737-8
  5. Cureus. 2025 Jul;17(7): e89172
      Pediatric acute lymphoblastic leukemia (ALL) poses significant treatment challenges, particularly in relapsed or refractory cases. This review synthesizes recent studies evaluating the safety and efficacy of chimeric antigen receptor T (CAR-T) cell therapy, specifically tisagenlecleucel, in achieving complete remission (CR) and improving overall survival rates among pediatric patients with ALL. A comprehensive literature search identified 12 studies published between January 2014 and July 2024, encompassing cohort studies and clinical trials. Findings indicate that CAR-T cell therapy demonstrates superior CR rates (up to 100% in some studies) and manageable safety profiles, with common adverse effects, including cytokine release syndrome (CRS) and neurotoxicity. This review points out some of the important aspects such as the identification of biomarkers for response prediction, understanding of the mechanisms of resistance, and the crucial requirement for long-term outcome data. Challenges remain in the management of adverse effects, particularly CRS and neurotoxicity. This review underscores the transformative potential of CAR-T cell therapy in pediatric oncology while emphasizing critical areas for further investigation to optimize patient outcomes and enhance the therapeutic landscape for pediatric ALL.
    Keywords:  car-t cell therapy; complete remission; cytokine release syndrome; overall survival; pediatric acute lymphoblastic leukemia; pediatric oncology
    DOI:  https://doi.org/10.7759/cureus.89172
  6. Adv Healthc Mater. 2025 Aug 29. e02930
      Chimeric antigen receptor (CAR) T cell therapies have shown clinical success in cancer treatment. However, the compositions of the final products can differ substantially between patients, leading to variable treatment responses. Recent studies suggest that CAR T cells manufactured from defined T cell subsets show greater potency and persistence and improved predictability of therapeutic efficacy. Current clinical-scale selection of T cell subsets relies on antibody-based magnetic activated cell sorting, which is costly and results in suboptimal product purity and yield, presenting a significant challenge for clinical translation. Here, a high-affinity CD62L aptamer and a traceless, sequential selection system are reported for the high-yield and high-purity isolation of CD62L⁺CD8⁺ T cells without residual selection labels. It is demonstrated that multiple aptamer-reversal agent pairs can be integrated into a magnetic platform for multi-parameter and high-throughput cell sorting. CAR T cells manufactured from aptamer-selected CD62L⁺CD8⁺ T cells, encompassing naïve and early memory CD8+ T cells, exhibit distinct phenotypic and functional advantages compared to those manufactured from bulk CD8+ T cells. This aptamer-based approach has the potential to improve the clinical efficacy of current adoptive T cell therapies by enabling precise and scalable selection of T cell subsets, with broad applications beyond T cell subset selection.
    Keywords:  CAR T cells; CD62L; aptamers; cell isolation; immunology
    DOI:  https://doi.org/10.1002/adhm.202502930
  7. Hum Gene Ther. 2025 Aug 29. 0
      Chimeric antigen receptor (CAR) T cell therapy has revolutionized treatment for hematological malignancies, yet translating this success to solid tumors remains challenging. Major obstacles include antigen heterogeneity, on-target off-tumor toxicity, limited infiltration and persistence, and the immunosuppressive tumor microenvironment (TME). The present review discusses recent engineering strategies designed to overcome these barriers. Innovations such as affinity-tuned and logic-gated CARs improve specificity and safety, while multi-antigen targeting helps address tumor heterogeneity by avoiding antigen escape. Gene-editing approaches enhance CAR T cell fitness by promoting memory phenotypes, metabolic resilience, and resistance to inhibitory signals imposed by the immunosuppressive TME. Additional modifications improve trafficking, enable extracellular matrix degradation, and reprogram CAR T cells to withstand the hostile conditions of the TME. Together, these advances reflect a growing shift toward rational CAR design and synthetic immunology, with the goal of achieving durable and safe responses in solid tumors. Early clinical trials show promise, and continued translational efforts will be key to unlocking the full therapeutic potential of CAR T cells in this setting.
    Keywords:  CAR T; TME; genetic engineering; solid tumors
    DOI:  https://doi.org/10.1177/10430342251372041
  8. Methods Mol Biol. 2025 ;2965 285-321
      Adoptive T-cell therapy is a promising cancer immunotherapy, but isolating tumor-specific cytotoxic T cells is time-consuming and often unsuccessful. An alternative approach involves genetically modifying T cells to express tumor antigen-specific T-cell receptors (TCRs) or chimeric antigen receptors (CARs), enabling the redirection of large numbers of immune cells to target malignant cells. CARs combine the specificity of antibody-derived single-chain variable fragments with T-cell signaling domains (e.g., CD3ζ, CD28, 4-1BB), enabling T cells to recognize and kill antigen-positive cancer cells in an MHC-independent manner. This chapter outlines protocols for large-scale T-cell expansion and medium-scale production of messenger RNA (mRNA) CAR-T cells using electroporation as a delivery method. Two CARs are used as model systems: one targeting CD19 and another targeting an antigen expressed on hematological malignancies and solid tumors.
    Keywords:  Chimeric antigen receptor; Gene therapy; T lymphocytes; mRNA electroporation
    DOI:  https://doi.org/10.1007/978-1-0716-4742-4_14
  9. Front Immunol. 2025 ;16 1625166
      CAR-T therapy, an innovative immunotherapeutic approach, genetically modifies T cells to express CARs, enabling targeted destruction of specific antigen-expressing cells. Initially developed for oncology, CAR-T therapy has shown significant potential in treating autoimmune diseases. By targeting CD19+ B cells, CAR-T therapy has demonstrated rapid and sustained remission in refractory cases, with studies showing normalized laboratory parameters and reduced disease activity. At the same time, CAR-NK, CAAR-T and CAR-Treg technologies further broaden therapeutic strategies. However, some adverse effects also exist, including CRS, ICANS and so on. Despite these challenges, CAR therapy represents a promising advancement in autoimmune disease treatment, with ongoing research aimed at enhancing efficacy, durability, and safety. Continuous innovation is essential to address limitations and optimize therapeutic outcomes.
    Keywords:  CAR (chimeric antigen receptor); SLE - systemic lupus erythematosus; adverse (side) effects; autoimmune diseases; chimeric antigen receptor T-cell therapy
    DOI:  https://doi.org/10.3389/fimmu.2025.1625166
  10. AAPS J. 2025 Sep 04. 27(6): 140
      CAR-T-cells can drive MHC class-I-mediated CD8 + cytotoxic T-cell response towards CAR constructs in addition to an antibody response. Immune response may also develop towards residuals present in the CAR-T cell product such as AAV, CRISPR/CAS9, and expamers. Health authorities recommend developing assays to assess both humoral and cellular immunogenicity towards the CAR-T protein. For the assessment of a humoral response, scientists can leverage the guidance and experience from anti-drug antibody (ADA) assays being developed for biologics. However, measuring CAR-T induced cellular immune responses may be challenging due to factors like cell survival, assay variability, lack of relevant positive controls, reagents, etc. This commentary overviews the strategy for investigating cellular immunogenicity for CAR-T products in development, describing the process for risk assessment, guidance on sample collection, including logistics of cell processing and handling, and design of CAR domain related peptides to elicit the memory response from dosed subjects. The experience gained from cellular immunogenicity assessments implemented for ongoing CAR-T-cell therapies and challenges encountered are presented with concrete recommendations, without disclosure of proprietary data. The clinical relevance/impact of assessing cellular immunogenicity for CAR-T therapies and any association with humoral response will also be delineated.
    Keywords:  CAR-T cells; ELISpot; IFN-γ; cytotoxic T-lymphocyte response; immunogenicity
    DOI:  https://doi.org/10.1208/s12248-025-01129-3
  11. Int J Mol Med. 2025 Nov;pii: 187. [Epub ahead of print]56(5):
      Chimeric antigen receptor (CAR) T cell therapy is a type of cellular immunotherapy showing promising clinical effectiveness and high precision. CAR‑T cells express membrane receptors with high specificity, which enable them to identify certain target antigens generated by cancerous cells. The three primary structural elements of the CAR are the extracellular domain, transmembrane domain and cytoplasmic domain. Nanobodies are a type of antibody fragment derived from the variable domains of camelid heavy chain antibodies (VHH), which are the antigen‑specific binding domains. They have high clinical applicability due to their tiny size, excellent target affinity, adaptable functions and guaranteed stability. Structurally pre‑designed nanobodies were transduced in primary T lymphocytes, forming CAR‑T cells and these have been demonstrated to have inhibitory effects on hematologic malignancy or solid tumor cells/tissues both in vivo and in vitro. At present, a number of novel nanobody‑based modalities can include a single nanobody, a bi‑valent nanobody and multivalent nanobody CAR‑T cells with bispecific and multispecific characteristics, showing promising therapeutic efficacy that is similar to CAR‑T cells modulated with a single‑chain variable fragment. Intriguingly, CAR‑T cells targeting the B‑cell maturation antigen modified using an anti‑B‑cell maturation antigen single nanobody or bivalent nanobody have been shown to exhibit clinical efficacy comparable to scFv‑modulated CAR‑T cells. The application of nanobodies in CAR‑T therapy has been well established from laboratory‑based evidence to clinical application and they have great potential for developing advanced CAR‑T cells for more complex employment.
    Keywords:  B‑cell maturation antigen; bispecific antibody; camelid heavy chain antibodies; chimeric antigen receptor‑T cells; nanobody
    DOI:  https://doi.org/10.3892/ijmm.2025.5628
  12. Oncoimmunology. 2025 Dec;14(1): 2546443
      CAR-based cell therapies have shown clinical success in treating various cancers, with CAR T cell therapies entering the clinical route and CAR NK cell therapies being evaluated in early-stage clinical trials. A key challenge is the presence of tumor-associated antigens on healthy cells, risking on-target off-tumor toxicities. Our comparative analysis of CAR T and CAR NK cells targeting the multiple myeloma-associated antigens BCMA, SLAMF7, and CD38 revealed that antigen density on target cells significantly modulates CAR NK cell activation and cytotoxicity. The cytotoxic potential of CAR NK cells was comparable to that of CAR T cells when targeting BCMA and CD38, but notable differences were observed in SLAMF7-directed CAR cells. While CAR sensitivity was similar in both cell types, CAR NK cell activity was balanced by inhibitory receptors like KIRs and NKG2A. This balance allows effective tumor control while potentially reducing on-target off-tumor effects on healthy cells with low antigen expression. Consequently, CAR NK cells offer greater flexibility in target antigen selection, potentially expanding the range of targetable antigens for cancer immunotherapy.
    Keywords:  CAR NK cells; CAR T cells; immunotherapy; on-target off-tumor cytotoxicity
    DOI:  https://doi.org/10.1080/2162402X.2025.2546443
  13. Immunotherapy. 2025 Sep 01. 1-8
      Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized hematological cancer treatment but faces challenges in solid tumors, including poor infiltration, cytokine release syndrome (CRS), and toxicity. CAR-T cell-derived exosomes (CAR-T exosomes) offer a promising alternative by inheriting CAR-mediated targeting and cytotoxic molecules (e.g., perforin, granzyme B), while avoiding issues such as CRS. Their nanoscale size enhances tumor penetration, and the lack of MHC reduces immunogenicity, which supports "off-the-shelf" applications. However, scalability remains limited by low yields from traditional isolation methods [e.g., ultracentrifugation (UC)], costly equipment, and inconsistent purification. This review summarizes recent advances in CAR-T exosome biology, scalable production strategies, and combinatorial approaches to overcome immunosuppressive tumor microenvironments (e.g., immune checkpoint inhibitors, cytokine modulation). We also discuss clinical prospects and future directions.
    Keywords:  CAR-T exosome therapy; cost optimization; exosome separation and purification; scale-up production; tumor treatment
    DOI:  https://doi.org/10.1080/1750743X.2025.2552105
  14. Hematology. 2025 Dec;30(1): 2550815
      Background: Chimeric antigen receptor (CAR)-T therapy has shown significant success in the treatment of relapsed or refractory acute lymphoblastic leukemia (r/r ALL). However, its role in patients with the TCF3-PBX1 fusion gene - which generally exhibit poor prognostic indicators - remains uncertain. Patients and methods: From September 2016 to March 2023, 7 patients with r/r ALL positive for the TCF3-PBX1 fusion gene underwent CD19 CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine. The safety and efficacy of the treatment were evaluated. Results: Four of the 7 patients experienced CAR-T-cell expansion in vivo, with a median peak percentage of CD3+ T-cell expansion of 64.9% (range: 29.1-78.1%). These 4 patients experienced grade 1 cytokine release syndrome. For the efficacy assessment, 4 patients with CAR-T-cell expansion achieved complete remission (CR), whereas the other 3 did not respond and ultimately died of disease progression. Among the 4 patients who achieved CR, 1 patient with a history of allogeneic stem cell transplantation (allo-HSCT) did not bridge to secondary allo-HSCT and relapsed 7 months after CAR-T-cell infusion. The other 3 CR patients successfully bridged to allo-HSCT; however, 2 of them relapsed post-allo-HSCT. One of the relapsed patients achieved remission after receiving donor-derived CAR-T-cell infusion and has maintained CR to date. Another patient died of disease progression. The remaining patient has achieved sustained remission to date. Conclusion: Our study indicates that CD19 CAR-T therapy is safe and effective in TCF3-PBX1-positive r/r B-ALL. Further studies in larger cohorts are warranted to confirm these observations .
    Keywords:  B-cell acute lymphoblastic leukemia; CD19 CAR-T; TCF3-PBX1 fusion gene; cytokine release syndrome; relapsed/refractory
    DOI:  https://doi.org/10.1080/16078454.2025.2550815
  15. Indian J Nephrol. 2025 Jul-Aug;35(4):35(4): 456-459
      Chimeric antigen receptor (CAR) T-cell therapy has recently evolved beyond cancer therapy's boundary to treating autoimmune diseases such as lupus nephritis. In CAR T-cell therapy, the genetically engineered patient's T cells express a receptor specifically targeting antigens such as CD19, a protein found on the surface of B cells. By directing the immune system to eliminate B cells, which play a central role in the pathogenesis of systemic lupus erythematosus, CAR T-cell therapy offers a novel and potent approach to resetting the immune system and achieving remission in difficult-to-treat lupus nephritis patients and many such conditions in nephrologists' practice.
    Keywords:  Autoimmune diseases; Cancer; Chimeric antigen receptor T-cell; Lupus nephritis
    DOI:  https://doi.org/10.25259/IJN_274_2024
  16. Methods Mol Biol. 2025 ;2965 275-284
      To redirect T cells toward target cells, they can be engineered ex vivo to express antigen-specific T cell receptors (TCRs), creating TCR-engineered T cells (TCR-T). In this chapter, we provide a streamlined protocol for generating autologous mRNA-electroporated, viral antigen-specific, immunosuppressive drug-resistant armored (IDRA) TCR-T cell therapy products in a laboratory setting. We also discuss the advantages of transient mRNA electroporation over permanent genetic modification technologies for our specific application. Finally, we present a protocol to evaluate the in vitro and in vivo functionality of our TCR-T cell therapy product.
    Keywords:  Adoptive T cell transfer; IDRA; TCR-T cell therapy; T cell in vitro expansion; Virus-specific T cells; mRNA electroporation
    DOI:  https://doi.org/10.1007/978-1-0716-4742-4_13
  17. J Immunol Methods. 2025 Aug 28. pii: S0022-1759(25)00170-X. [Epub ahead of print]544 113970
       BACKGROUND: Chimeric Antigen Receptor (CAR)-T cell therapy is a highly innovative form of cell-based immunotherapy. To expand CAR-T therapies into additional disease indications, identification of novel tumor antigens and grafting of CARs on other types of immune cells, such as macrophages and natural killer (NK) cells are being pursued. Therefore, as this treatment modality continues to evolve, there is a need for highly specific detection reagents to interrogate CAR surface expression.
    METHODS/OBJECTIVES: This study uses flow cytometry to compare the ability of various commercially available CAR detection reagents' to detect CAR constructs containing distinct hinges, linker sequences, and scFv designs. Furthermore, interrogation off-target interactions were performed within a PBMC matrix.
    RESULTS: All antibody-based CAR detection reagents demonstrated specificity and robust signal in stable CAR-Jurkat cell lines and primary human CAR-T cells. Protein L only detected anti-CD20 (Leu16) scFv-based CAR; off-target non-CAR staining was observed in non-transduced human PBMCs. Detection using recombinant protein antigen provides clean results in single-stain samples for CD19 and BMCA proteins, though CD20 did not produce positive staining in anti-CD20 CARs. Additionally, in live human PBMCs, false-positive signals may be observed for antibody conjugates due to the binding of human Fc receptors to IgG.
    CONCLUSIONS: CAR idiotype antibodies, recombinant antigens, and anti-linker antibodies were able to provide specific and robust detection of CAR-expressing cells. However, the utility of both idiotype antibodies and recombinant antigens is limited to CARs targeting specific antigens. The anti-linker antibodies enable universal and broad detection of CARs independent of target antigens.
    Keywords:  CAR; Detection; Flow cytometry; G4S; Whitlow
    DOI:  https://doi.org/10.1016/j.jim.2025.113970
  18. Stem Cell Rev Rep. 2025 Sep 04.
      Hematopoietic stem cell transplantation is an important treatment for hematological malignancy and disorders, but is fraught with high risks, including graft-versus-host disease, infection, and relapse. Recent evidence now identifies that the microbiome plays a significant role in influencing transplant outcomes, in which microbial dysbiosis-defined by reduced diversity and pathogen overgrowth-is linked to greater complications and death. Microbiome manipulation with approaches including beneficial microbial species, fiber, fecal transplants, and diet has the potential to mitigate these risks. Experiments show that the restoration of beneficial microbes can restore immunity, reduce graft-versus-host disease severity, and reduce infection. Some challenges remain, including standardization of protocols, long-term efficacy, and safety in immunocompromised recipients. Future research will be focused on mechanisms, trials, and new technology for microbiome-based therapy, with the ultimate goal of improving survival and quality of life for transplant recipients. Hereupon, this review addresses how microbiome engineering can revolutionize cancer treatment by optimizing gut microbial communities for better outcomes in hematopoietic stem cell transplantation (HSCT).
    Keywords:  Bone marrow transplantation; Cancer care; Graft-versus-host disease; Gut microbiome; Microbiome engineering
    DOI:  https://doi.org/10.1007/s12015-025-10958-w
  19. Small. 2025 Sep 01. e06429
      Chimeric antigen receptor (CAR)-T cell immunotherapy has emerged as a groundbreaking approach in cancer treatment, offering new hope across various malignancies. However, its success against solid tumors remains limited due to critical challenges, including off-tumor, on-target toxicity, immune resistance, poor T cell infiltration into the tumor microenvironment (TME), and T cell exhaustion. In response, interdisciplinary innovations in synthetic biology and biomaterials are redefining how can be engineer smarter, more responsive CAR-T cells. Recent advances have introduced biomaterials not only as precision delivery vehicles but also as artificial antigen-presenting cells (APCs), high-throughput screening platforms, and tools to replicate the complex biomechanical landscape of the TME. This review highlights these cutting-edge strategies, emphasizing how biomaterials and synthetic circuits can aid studies and strategies to enhance CAR-T cell efficacy in solid tumors while minimizing adverse effects. Future directions at the intersection of tumor-inspired biomaterials and T cell engineering, envisioning a new generation of CAR-T therapies tailored to overcome the formidable barriers of the TME are also explored.
    Keywords:  CAR‐T; biomaterials; delivery systems; ex vivo mechanical models; immunotherapy; solid tumor microenvironment; synthetic biology
    DOI:  https://doi.org/10.1002/smll.202506429
  20. J Drugs Dermatol. 2025 Sep 01. 24(9): 949-951
      The "Sephora Kids" trend, where children, especially tweens and teens, are increasingly using makeup and skincare products marketed by beauty retailers, presents notable dermatological challenges. Although these products can facilitate self-expression and teach self-care, their safety and efficacy for young users are largely unverified. This review examines 4 key ingredients commonly found in these products,retinol, exfoliating acids (AHA and BHA), and vitamin C, to assess their implications for pediatric skincare. Current literature and FDA-approved guidelines indicate that these ingredients have not been thoroughly tested in children. Consequently, using these products without medical supervision can pose risks such as skin redness, irritation, heightened sun sensitivity, dermatitis, and other potential adverse effects. This review underscores the importance of cautious use and highlights the need for further research to ensure the safety of these ingredients in young populations. By informing healthcare providers and consumers of these risks, we aim to promote safer skincare practices among children.
    DOI:  https://doi.org/10.36849/jdd.8800
  21. Nat Rev Drug Discov. 2025 Sep 02.
      
    Keywords:  Biotechnology; Cancer; Drug discovery; Immunology; Therapeutics
    DOI:  https://doi.org/10.1038/d41573-025-00143-6
  22. Drug Des Devel Ther. 2025 ;19 7493-7502
       Introduction: The use of Artificial intelligence in drug discovery is changing the field of Medicine across the world today positively. In this review, the role of AI in each focus area for the improvement of the drug development process, and its relevance in translational medicine is discussed.
    Materials and Method: A systematic review was conducted by searching databases such as PubMed and Scopus, employing key terms like "AI" "drug discovery" "machine learning" "clinical trials" and "translational medicine." Inclusion criteria focused on peer-reviewed studies published between 2014 and 2024 that specifically addressed the role of AI in drug development. Data extraction involved categorizing findings based on different phases of drug discovery.
    Results: The findings reveal that the use of AI lowers costs, shortens the time required for drug development, and enhances the predictive capability. AI technologies play an essential role in molecular modeling, drug design and screening, and the efficient design of clinical trials. However, some of the issues that remain include the quality of available data, issues of interpretability of the models, and the more critical issue of ethical considerations that need collective efforts on the development of associate regulatory policies.
    Conclusion: AI holds immense potential to dramatically change and transform the process of drug discovery and translational medicine while promoting accurate prevention and cures. However, it is also important to understand how to work with existing problems to make the best use of AI in healthcare. The roles of AI technologies are likely to grow in the development of the medical future, provide patients with better results, and stimulate the innovations in the field of the drug creation.
    Keywords:  artificial intelligence; clinical trials; drug development; machine learning; personalized treatment; translational medicine
    DOI:  https://doi.org/10.2147/DDDT.S538269
  23. Acta Med Port. 2025 Aug 27.
      Clostridioides difficile is an opportunistic pathogen that can cause a range of conditions, from asymptomatic carriage to severe illness, posing a significant public health threat due to its high mortality rates and substantial healthcare costs. Traditional treatment options, including antibiotics, often fail to eradicate the infection, leading to recurrent cases that severely impact patients' lives. Intestinal microbiota transplant (IMT) has emerged as an effective strategy for decolonizing pathogenic agents, demonstrating safety and efficacy, particularly in treating recurrent Clostridioides difficile infection (rCDI). Despite its potential, access to IMT is limited due to safety concerns, logistical challenges, and a lack of proper guidance, underscoring the urgent need for structured intestinal microbiota banks (IMBs). These organized facilities are crucial for the collection, screening, processing, and distribution of intestinal microbiota preparations, thereby facilitating the clinical application of IMT. In this narrative review, we discuss the relevance of applying IMT for the treatment of rCDI in Europe, with a focus on Portugal. We highlight the existence and distribution of IMBs across Europe and their importance in improving access to IMT. This review also addresses the challenges in creating an IMB and the development of such a structure in Portugal as a centralized repository for high-quality, standardized microbiota preparations, making IMT accessible for national hospitals. Additionally, it emphasizes the need to raise awareness among healthcare providers and the public to support the broader adoption of IMT.
    Keywords:  Clostridioides difficile; Clostridium Infections; Europe; Fecal Microbiota Transplantation; Gastrointestinal Microbiome
    DOI:  https://doi.org/10.20344/amp.22750
  24. Hematology. 2025 Dec;30(1): 2549159
       OBJECTIVE: This systematic review aims to evaluate the extensive application of platelet-rich plasma (PRP) as a novel autologous cell therapy across various clinical disciplines in recent years.
    METHOD: A comprehensive search was conducted across PubMed, Scopus, Embase, and the Cochrane Library from 2009 to 2024, resulting in the identification of 153 research articles. The inclusion criteria were focused on studies that reported on the molecular mechanisms of action and clinical efficacy. The data were synthesized through qualitative narrative analysis and thematic classification.
    RESULT: Key active components found in PRP, including platelet-derived growth factor, transforming growth factor-β, and vascular endothelial growth factor, exhibit regulatory effects on fibroblasts, endothelial cells, and immune cells. These components facilitate cell proliferation and migration via signaling pathways such as PI3 K/Akt and MAPK/ERK. Notably, differences exist between the use of PRP alone versus its application in combination therapies for conditions such as bone and ligament repair, female infertility, alopecia, facial rejuvenation, diabetic foot ulcers, and fistulas. Factors such as PRP storage methods, white blood cell concentration levels, platelet concentration variations, and whether it is activated ex vivo can significantly influence therapeutic outcomes.
    CONCLUSION: PRP represents a highly promising autologous treatment modality. Standardizing protocols for PRP preparation alongside disease-specific treatment strategies will enhance precision in clinical applications.
    Keywords:  Clinical applications; Mechanism of action; Platelet-rich plasma (PRP)
    DOI:  https://doi.org/10.1080/16078454.2025.2549159
  25. Cancer Treat Rev. 2025 Aug 25. pii: S0305-7372(25)00138-0. [Epub ahead of print]140 103016
      Immunogenicity of a therapeutic protein product may elicit an unintended immune response, and is a critical aspect evaluated in oncology clinical trials. The development of anti-drug antibodies (ADAs) can impact the pharmacokinetics, pharmacodynamics, efficacy, and safety of these therapies. We review the background and nomenclature of immunogenicity assessment in oncology studies and emphasize the complexities in ADA detection arising from assay sensitivity, drug interference, and notably, the frequency of patient sampling for ADA analysis. The applicability of common nomenclature, however, has limitations in the context of oncology. Of prime consideration for physicians is that the clinical impact of ADA is far more important than just their presence. Furthermore, the interpretation of immunogenicity data in oncology is complicated by patient-specific factors, concomitant treatments, and potential survivorship bias. Regulatory guidelines acknowledge these complexities, mandating specific statements on product labels cautioning against cross-trial comparisons of ADA incidence due to variations in assay methods and sampling schedules. Accurate interpretation of immunogenicity data, considering assay methodologies, study design, and sampling frequency, is crucial for clinicians to assess the clinical relevance of ADA findings and make informed treatment decisions for patients receiving therapeutic protein products in oncology. The focus should be on the clinical relevance of ADAs rather than simply their incidence.
    DOI:  https://doi.org/10.1016/j.ctrv.2025.103016
  26. F1000Res. 2024 ;13 253
      Digital transformation has been one of the main trends in organizations in recent years, and digital literacy is a critical factor in the success of this transformation. Digital transformation involves the use of digital technologies to improve an organization's processes, products, and services. For this transformation to be successful, it is necessary for employees to have knowledge of and skills in digital technologies. Digital literacy allows employees to understand technologies and their applications, know how to use them efficiently and safely, evaluate and select the most appropriate digital tools for each task, and be prepared to deal with problems and challenges that arise in the digital environment. This study investigates the relationship between digital transformation and digital literacy through a Systematic Literature Review conducted in accordance with Kitchenham's guidelines. A total of 54 articles, published from 2018, were analyzed from databases such as Scopus, Science Direct, IEEE and Springer. The results reveal that digital literacy significantly influences the success of digital transformation, particularly in areas such as employee adaptability, innovation capacity, and digital tool integration. Key mediating and moderating factors identified include organizational learning culture, leadership support, ongoing training programs, and technological infrastructure. Based on these findings, an explanatory model was developed that maps the interaction between these variables and their impact on digital transformation outcomes. The study offers practical implications for organizations seeking to enhance their digital maturity: investing in employee digital literacy development, aligning leadership strategies with digital initiatives, and fostering a supportive culture for digital adoption are crucial steps. Thus, this study is relevant because it seeks to understand how digital literacy can impact Digital Transformation in organizations and, through the construction of an explanatory model, allows the identification of variables that influence this relationship by developing strategies to improve the digital literacy of employees in organizations.
    Keywords:  Digital Literacy; Digital Transformation; Explanatory Models; Systematic Literature Review
    DOI:  https://doi.org/10.12688/f1000research.146991.2
  27. Neuromolecular Med. 2025 Sep 05. 27(1): 63
      Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues, affecting millions of people and often requiring long-term treatment. Current therapies, such as immunosuppressants and biologics, help manage symptoms but can cause serious side effects. A promising new approach involves engineered microbiota-a method that modifies gut bacteria to influence immune function and potentially ease autoimmune conditions. The gut microbiome is crucial in regulating immunity, and imbalances in its composition have been linked to diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD). Engineered microbiota works by altering microbial communities, either by adding new strains, genetically modifying existing bacteria, or using carefully selected groups of microbes to control inflammation and immune responses. Recent studies in both animal models and human trials suggest this approach could help restore immune tolerance, reduce inflammation, and repair the gut barrier. However, challenges remain, including ensuring safety, long-term effectiveness, and meeting regulatory standards. Despite being in its early stages, engineered microbiota holds great promise as a future treatment for autoimmune diseases, paving the way for more precise and personalized therapies that leverage the power of the microbiome to improve health.
    Keywords:  Autoimmune diseases; Engineered microbiota; Gut microbiota; Immune system
    DOI:  https://doi.org/10.1007/s12017-025-08879-5