Fueling CARs: metabolic strategies to enhance CAR T-cell therapy.

Autor: Van der Vreken A; Translational Oncology Research Center, Team Hematology and Immunology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium., Vanderkerken K; Translational Oncology Research Center, Team Hematology and Immunology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium., De Bruyne E; Translational Oncology Research Center, Team Hematology and Immunology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium., De Veirman K; Translational Oncology Research Center, Team Hematology and Immunology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium., Breckpot K; Translational Oncology Research Center, Team Laboratory of Cellular and Molecular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium., Menu E; Translational Oncology Research Center, Team Hematology and Immunology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium. Eline.Menu@vub.be.
Jazyk: angličtina
Zdroj: Experimental hematology & oncology [Exp Hematol Oncol] 2024 Jul 10; Vol. 13 (1), pp. 66. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1186/s40164-024-00535-1
Abstrakt: CAR T cells are widely applied for relapsed hematological cancer patients. With six approved cell therapies, for Multiple Myeloma and other B-cell malignancies, new insights emerge. Profound evidence shows that patients who fail CAR T-cell therapy have, aside from antigen escape, a more glycolytic and weakened metabolism in their CAR T cells, accompanied by a short lifespan. Recent advances show that CAR T cells can be metabolically engineered towards oxidative phosphorylation, which increases their longevity via epigenetic and phenotypical changes. In this review we elucidate various strategies to rewire their metabolism, including the design of the CAR construct, co-stimulus choice, genetic modifications of metabolic genes, and pharmacological interventions. We discuss their potential to enhance CAR T-cell functioning and persistence through memory imprinting, thereby improving outcomes. Furthermore, we link the pharmacological treatments with their anti-cancer properties in hematological malignancies to ultimately suggest novel combination strategies.
(© 2024. The Author(s).)
Databáze: MEDLINE
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