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

Autor: Arne Van der Vreken, Karin Vanderkerken, Elke De Bruyne, Kim De Veirman, Karine Breckpot, Eline Menu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Experimental Hematology & Oncology, Vol 13, Iss 1, Pp 1-17 (2024)
Druh dokumentu: article
ISSN: 2162-3619
DOI: 10.1186/s40164-024-00535-1
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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