CAR-T细胞治疗实体瘤的挑战与思考

Chimeric antigen receptor T cell based therapeutic modality in solid tumors

针对CD19靶点的嵌合抗原受体(chimeric antigen receptor,CAR)T细胞在B细胞恶性血液系统肿瘤治疗中取得的成功,证实了抗原特异性靶向免疫细胞对肿瘤治疗的临床价值。同时这一发现也激发了CAR-T细胞技术的拓展应用性研究,多项CART细胞治疗实体瘤的临床前研究和临床研究正在开展。然而实体肿瘤和血液肿瘤本身特质上的差异决定了这种治疗模式必须重新斟酌细胞治疗本身的特点、作用规律等因素。本文讨论了CAR-T细胞治疗实体瘤相关的安全性管控措施、肿瘤靶点选择、预处理及联合治疗,并通过相关的实践经验展望该治疗方式的未来发展方向。

The CD19-targeted chimeric antigen receptor （CAR） T-cell treatment has achieved clinical success in treating B-cell lineage hematopoietic malignancies. This accomplishment involved the precise and efficient elimination of tumor cells by tumor-associated an- tigen-redirected immune cells. As a result, the reinitiation of several CAR T-cell （CART） based clinical trials in solid tumors was promot- ed. However, developing a feasible and efficient CAR T based therapeutic modality for solid tumors is urgently needed given the differ- ential properties between liquid and solid tumors. In this review, we discuss the advances in the management of cytotherapeutic modality for solid tumors. The aspects considered include toxicity management, target selection, and primer or conditioning treatment.