嵌合抗原受体T（chimeric antigen receptor T cells，CAR-T）细胞已从实验室走向了临床试验，在治疗B细胞恶性肿瘤中取得了显著疗效，但在探索CAR-T细胞治疗恶性肿瘤的临床研究中，仍面临不少困难与挑战：难以找到肿瘤特异性的靶点，以克服其脱靶效应（on-target off tumor effect）；在治疗实体瘤中CAR-T细胞很难达到肿瘤部位，以改善免疫抑制微环境发挥作用；CAR-T细胞在清除肿瘤细胞的同时也会杀伤表达相同靶点的正常细胞；针对除B细胞肿瘤之外的血液肿瘤以及实体瘤而言，CAR-T细胞的有效性还有待提高。本文重点介绍如何通过CAR-T细胞结构的优化使得CAR-T细胞能够精准地识别肿瘤细胞，克服肿瘤的免疫抑制微环境来提高CAR-T细胞治疗恶性肿瘤的有效性；同时使得CAR-T细胞可以被更好地控制，使得CAR-T细胞的安全性更高。

hard to reach the tumor positions and to improve their immunosuppressive microenvironment. When the CAR-T cells eliminate tumor cells, at the same time they also kill normal cells with the same target points. Efficacy of the CAR-T cells therapy for hematologic tumors and solid tumors except B cell tumors still needs to be improved. This paper focuses on that how the CAR-T cells could accurately identify tumor cells via optimization of the CAR-T cell structures and that effectiveness of the CAR-T cell therapy for malignant tumors could be enhanced through overcoming immunosuppressive microenvironment of tumors. At the same time, the CAR-T cells could be better controlled and safety of the CAR-T cells higher.

首都临床特色应用研究与成果推广项目（No. Z161100000516184）