CAR-T疗法及其在肿瘤免疫治疗中的应用进展

Advances of CAR-T Immunotherapy for Cancer

嵌合抗原受体T(chimeric antigen receptor T,TCAR-T)细胞免疫疗法是通过赋予T细胞非HLA依赖性的方式来识别肿瘤抗原能力的,改造的T细胞相较于天然T细胞表面受体TCR能够识别更广泛的靶标。在急性白血病和非霍奇金淋巴瘤的治疗上取得了显著的疗效。最近,包括诺华公司的CTL019在内多个CAR-T产品被FDA批准上市。近几年,CAR-T疗法在脑胶质瘤、前列腺癌、肺癌等实体瘤方面的研究也取得了巨大的进展,被认为是最有前景的肿瘤治疗方式之一。该文主要就CAR-T的发展、临床应用及其面临的挑战与未来的发展方向作一综述。

Chimeric antigen receptor T （CAR-T） cell immunotherapy is a method for engineering recombinant immunoreceptor based on an antibody-derived fragment which endows T cells with the ability to recognize specifically tumor-associated antigens （TAA） with independence of the expression of major histocompatibility complex （MHC） molecules. Clinical trials of CAR-T cells therapy for relapsed or refractory B cell malignancies have demonstrated impressive results. As a milestone, recently a Novartis product--CTL019 is approved by the US FDA for such malignancies. Besides the blood malignancies, CAR-T immunotherapy in treatment of glioblastoma, prostate cancer NSCLC, and other solid tumors also made progress. The immunotherapy is becoming one of the most promising cancer therapy. In this article, we focus on the major challenges in the further development and strategies for increasing anti-tumor activity and safety.