肿瘤细胞治疗研究
英文原题：The mechanisms and countermeasures for CAR-T cell expansion and persistence deficiency.
嵌合抗原受体（CAR）T 细胞疗法已成为血液系统恶性肿瘤，尤其是 B 细胞恶性肿瘤的开创性治疗。
嵌合抗原受体（CAR）T细胞疗法已成为血液系统恶性肿瘤，特别是B细胞恶性肿瘤的一项突破性治疗。然而，在慢性淋巴细胞白血病（CLL）和急性髓系白血病（AML）等恶性肿瘤中，复发风险高、疗效有限，限制了该疗法的临床应用。CAR-T细胞的扩增、浸润和持久性是决定其疗效的关键因素。已知扩增有限和持久性不足是未能缓解及早期复发的重要原因，因此亟需阐明其机制并探索应对措施。本综述介绍CAR-T细胞在多种血液系统恶性肿瘤和实体瘤中的扩增与持久性特征，并综述CAR-T细胞扩增和持久性不足的现有机制认识，重点讨论CAR-T细胞内在缺陷及其与全身和局部免疫环境的相互作用。最后，我们总结了通过改善CAR-T细胞质量并克服免疫抑制环境来增强其扩增和持久性的方法。
Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for hematological malignancies, particularly B-cell malignancies. However, its high risk of relapse and low efficacy in malignancies such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) have limited its clinical utility. The expansion, infiltration and persistence of CAR-T cells are key determinants of their efficacy. It has been recognized that limited expansion and lack of persistence are major contributors to non-remission and early relapse, highlighting the need to elucidate their mechanisms and countermeasures. In this review, we described features of CAR-T cell expansion and persistence in various hematogenic malignancies and solid tumors. Then, current knowledge on the mechanisms underlying deficiency in CAR-T cell expansion and persistence is presented, focusing on the intrinsic deficiency of CAR-T cells as well as their interaction with the systemic and local immune environment. Finally, we summarize approaches to enhance CAR-T cell expansion and persistence by improving CAR-T cell quality and overcoming the immunosuppressive environment.
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