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Adoptive cellular therapies have revolutionized the management of hematologic malignancies, particularly lymphoma and multiple myeloma. These therapies targeting disease-specific antigens, such as CD19 in lymphoma and B cell maturation antigen in multiple myeloma, are efficacious and well-tolerated compared with conventional chemotherapies. Unfortunately, their potential remains unrealized in acute myeloid leukemia (AML). This is because most targetable antigens on AML cells are also expressed on healthy myeloid hematopoietic stem cells (HSC). Therefore, targeting them results in severe myeloablative effects and pancytopenia. Several strategies have been devised to overcome this barrier, including identifying AML-specific antigens, limiting CAR-T cell persistence to prevent prolonged myeloablation, and creating AML-specific antigens through manipulating HSCs prior to allogenic transplant. In this review, we discuss these strategies and the ongoing clinical trials on adoptive cellular therapies in AML, limiting our focus to chimeric antigen receptor-T cells (CAR-T) and chimeric antigen receptor-natural killer cells (CAR-NK).
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http://dx.doi.org/10.56875/2589-0646.1060 | DOI Listing |
Am J Transplant
September 2025
Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School; Department of Surgery, Massachusetts General Hospital, Harvard Medical School; Department of Surgery, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania
Achieving immune tolerance is a key goal in organ transplantation, as it eliminates the need for long-term immunosuppression. Regulatory B cells (Bregs) present a promising strategy for inducing tolerance. Our previous findings demonstrate that the adoptive transfer of ex vivo-expanded murine splenic B regulatory cells, referred to as TLR-Bregs (TLR9/TLR4 stimulation), induces tolerance to allografts.
View Article and Find Full Text PDFPathol Res Pract
September 2025
Department of Biotechnology, Delhi Technological University, India. Electronic address:
The intricate interplay between cancer and autoimmune diseases (ADs) is rooted in immune dysregulation, where genetic susceptibility, chronic inflammation, epigenetic modifications, and immunosuppressive therapies contribute to tumorigenesis. The dualistic nature of immune activation complicates therapeutic strategies, as immune checkpoint inhibitors and other immune-stimulatory therapies may exacerbate underlying ADs, leading to immune-related adverse events (irAEs), including organ toxicity, dermatologic reactions, and disease flares. Conversely, immunosuppressive treatments aimed at controlling ADs can compromise anti-tumor immunity and reduce the efficacy of cancer therapies.
View Article and Find Full Text PDFBiotechnol J
September 2025
Department of Biochemical Engineering, University College London, London, UK.
Chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated clinical efficacy in treating haematological malignancies, resulting in multiple regulatory approvals. However, there is a need for robust manufacturing platforms and the use of GMP-aligned reagents to meet the clinical and commercial demands. This study investigates the impact of serum/xeno-free medium (SXFM) and cytokine supplementation on CAR-T cell production in static and agitated culture systems, using 24-well plate G-Rex vessels and 500 mL stirred tank bioreactors (STRs), respectively.
View Article and Find Full Text PDFEur J Immunol
September 2025
Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
Memory T cells, a sizable compartment of the mature immune system, enable enhanced responses upon re-infection with the same pathogen. We have recently shown that virus-experienced innate acting T (T) cells can modulate infectious or autoimmune diseases through TCR-independent IFN-γ production. However, how these cells arise remains unclear.
View Article and Find Full Text PDFAdv Pharm Bull
July 2025
Department of Biotechnology and Bioinformatics, North-Eastern Hill University, Shillong, India 793022.
One of the major reason of deaths due to cancer globally is caused by lung cancer of which the two main types include non-small cell and small cell lung cancer. The onset of treatment-resistance in cancer cells offers a serious obstacle to the therapeutic effect despite that primary conventional treatments have provided significant benefits and cures. Cancer immunotherapy offers a compelling alternative in patients by utilizing their immune system to enhance its ability to fight against tumors.
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