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嵌合抗原受体 T 细胞(CAR-T)免疫疗法治疗实体瘤:经验教训与前进策略。

Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward.

机构信息

School of Medicine, Chengdu University, Chengdu, 610106, China.

UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK.

出版信息

J Hematol Oncol. 2018 Feb 13;11(1):22. doi: 10.1186/s13045-018-0568-6.

Abstract

Recently, the US Food and Drug Administration (FDA) approved the first chimeric antigen receptor T cell (CAR-T) therapy for the treatment CD19-positive B cell acute lymphoblastic leukemia. While CAR-T has achieved remarkable success in the treatment of hematopoietic malignancies, whether it can benefit solid tumor patients to the same extent is still uncertain. Even though hundreds of clinical trials are undergoing exploring a variety of tumor-associated antigens (TAA), no such antigen with comparable properties like CD19 has yet been identified regarding solid tumors CAR-T immunotherapy. Inefficient T cell trafficking, immunosuppressive tumor microenvironment, suboptimal antigen recognition specificity, and lack of safety control are currently considered as the main obstacles in solid tumor CAR-T therapy. Here, we reviewed the solid tumor CAR-T clinical trials, emphasizing the studies with published results. We further discussed the challenges that CAR-T is facing for solid tumor treatment and proposed potential strategies to improve the efficacy of CAR-T as promising immunotherapy.

摘要

最近,美国食品和药物管理局(FDA)批准了首个用于治疗 CD19 阳性 B 细胞急性淋巴细胞白血病的嵌合抗原受体 T 细胞(CAR-T)疗法。虽然 CAR-T 在治疗血液恶性肿瘤方面取得了显著的成功,但它是否能在同等程度上使实体瘤患者受益尚不确定。尽管正在进行数百项临床试验以探索各种肿瘤相关抗原(TAA),但对于实体瘤 CAR-T 免疫治疗,尚未发现与 CD19 具有可比特性的此类抗原。目前,CAR-T 治疗实体瘤的主要障碍包括 T 细胞运输效率低下、免疫抑制性肿瘤微环境、抗原识别特异性不佳以及缺乏安全控制。在此,我们回顾了实体瘤 CAR-T 的临床试验,重点介绍了已发表结果的研究。我们进一步讨论了 CAR-T 在实体瘤治疗上面临的挑战,并提出了一些潜在的策略,以提高 CAR-T 作为一种有前途的免疫疗法的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e998/5809840/8558e66b61f8/13045_2018_568_Fig1_HTML.jpg

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