CAR T细胞广泛应用于复发性血液肿瘤患者。六种细胞疗法获得批准，针对多发性骨髓瘤和其他 B 细胞恶性肿瘤，出现了新的见解。深入的证据表明，CAR T 细胞治疗失败的患者除了抗原逃逸之外，其 CAR T 细胞的糖酵解程度更高，代谢更弱，并且寿命较短。最近的进展表明，CAR T 细胞可以通过代谢工程进行氧化磷酸化，从而通过表观遗传和表型变化来延长其寿命。在这篇综述中，我们阐明了重新连接其代谢的各种策略，包括 CAR 结构的设计、共刺激选择、代谢基因的遗传修饰和药理学干预。我们讨论了它们通过记忆印记增强 CAR T 细胞功能和持久性的潜力，从而改善结果。此外，我们将药物治疗与其在血液恶性肿瘤中的抗癌特性联系起来，最终提出新的联合策略。© 2024。作者。

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).