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针对实体瘤的嵌合抗原受体 T 细胞(CAR-T)癌症免疫疗法面临的障碍。

Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.

Department of Emergency, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

Sci China Life Sci. 2016 Apr;59(4):340-8. doi: 10.1007/s11427-016-5027-4. Epub 2016 Mar 11.

Abstract

Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

摘要

最近关于嵌合抗原受体 (CAR) 修饰 T 细胞对抗血液恶性肿瘤的显著疗效的报告激发了肿瘤学家将这些努力扩展到治疗实体瘤。CAR-T 细胞为基础的癌症免疫疗法治疗实体瘤的临床试验表明,疗效不如血液恶性肿瘤显著。在使用 CAR-T 细胞治疗实体癌时,研究人员必须面对几个挑战,包括选择理想的靶标、促进有效的迁移和浸润、克服免疫抑制微环境以及避免相关毒性。在这篇综述中,我们讨论了实体瘤对 CAR-T 细胞为基础的免疫疗法的限制因素,以及为提高这种方法的治疗潜力而采用的策略。未来需要进一步的研究来提高治疗效果,降低 CAR-T 细胞治疗实体恶性肿瘤患者的不良反应。

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