The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) through genetic engineering is one of the most promising new therapies for treating cancer patients. A robust CAR T cell-mediated anti-tumor response requires the coordination of nutrient and energy supplies with CAR T cell expansion and function. However, the high metabolic demands of tumor cells compromise the function of CAR T cells by competing for nutrients within the tumor microenvironment (TME). To substantially improve clinical outcomes of CAR T immunotherapy while treating solid tumors, it is essential to metabolically prepare CAR T cells to overcome the metabolic barriers imposed by the TME. In this review, we discuss a potential metabolism toolbox to improve the metabolic fitness of CAR T cells and maximize the efficacy of CAR T therapy.
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http://dx.doi.org/10.3389/fonc.2019.00322 | DOI Listing |
Sci Adv
January 2025
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.
View Article and Find Full Text PDFInt Immunol
January 2025
Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4, Sakamoto, Nagasaki, 852-8523, Japan.
Since the first approval of an immune-checkpoint inhibitor, we have witnessed the clinical success of cancer immunotherapy. Adoptive T-cell therapy with chimeric antigen-receptor T (CAR-T) cells has shown remarkable efficacy in hematological malignancies. Concurrently with these successes, the cancer immunoediting concept that refined the cancer immunosurveillance concept underpinned the scientific mechanism and reason for past failures, as well as recent breakthroughs in cancer immunotherapy.
View Article and Find Full Text PDFACS Appl Bio Mater
January 2025
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad 500037, India.
Immunotherapy is a cutting-edge approach that leverages sophisticated technology to target tumor-specific antibodies and modulate the immune system to eradicate cancer and enhance patients' quality of life. Bioinformatics and genetic science advancements have made it possible to diagnose and treat cancer patients using immunotherapy technology. However, current immunotherapies against cancer have limited clinical benefits due to cancer-associated antigens, which often fail to interact with immune cells and exhibit insufficient therapeutic targeting with unintended side effects.
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January 2025
Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy.
Despite the advances of CAR-T cells in certain hematological malignancies, mostly from B-cell derivations such as non-Hodgkin lymphomas, acute lymphoblastic leukemia and multiple myeloma, a significant portion of other hematological and non-hematological pathologies can benefit from this innovative treatment, as the results of clinical studies are demonstrating. The clinical application of CAR-T in the setting of acute T-lymphoid leukemia, acute myeloid leukemia, solid tumors, autoimmune diseases and infections has encountered limitations that are different from those of hematological B-cell diseases. To overcome these restrictions, strategies based on different molecular engineering platforms have been devised and will be illustrated below.
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January 2025
DIMEAS, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129 Torino, Italy.
Haematological malignancies comprise a diverse group of life-threatening systemic diseases, including leukaemia, lymphoma, and multiple myeloma. Currently available therapies, including chemotherapy, immunotherapy, and CAR-T cells, are often associated with important side effects and with the development of drug resistance and, consequently, disease relapse. In the last decades, it was largely demonstrated that the tumor microenvironment significantly affects cancer cell proliferation and tumor response to treatment.
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