Department of Research and Development, Shenzhen Institute for Innovation and Translational Medicine, Shenzhen International Biological Valley-Life Science Industrial Park, Dapeng New District, Shenzhen, China.
Department of Oncology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
Immunol Lett. 2019 Dec;216:51-62. doi: 10.1016/j.imlet.2019.10.002. Epub 2019 Oct 6.
Adoptive transfer of T cells genetically engineered with chimeric antigen receptors (CAR-T cells) have proven to be highly effective for treating CD19 B cell-derived hematologic malignancies. However, due to the lack of ideal tumor surface antigens, CAR-T cell therapy has limited success in treating solid tumors. T cells genetically engineered with T cell receptors (TCR-T cells) recognize intracellular and cell-surface antigens in the context of major histocompatibility complex (MHC) presentation and thus have the potential to access much more target antigens than CAR-T cells, providing great promise in treating solid tumors. There is an increasing interest in the application of TCR-T cell therapy for solid tumors, and fifty-six clinical trials are undergoing worldwide to confirm its validity. In this review, we summarize the recent progress in clinical studies of TCR-T cell therapy, describe strategies in the preparation and characterization of TCR-T cells, focusing on antigen selection, TCR isolation and methods to further enhance the potency of adoptively transferred cells.
嵌合抗原受体(CAR)修饰的 T 细胞(CAR-T 细胞)过继转移已被证明对治疗 CD19 B 细胞来源的血液恶性肿瘤非常有效。然而,由于缺乏理想的肿瘤表面抗原,CAR-T 细胞治疗在治疗实体瘤方面的成功率有限。T 细胞受体(TCR)修饰的 T 细胞(TCR-T 细胞)在主要组织相容性复合体(MHC)呈递的情况下识别细胞内和细胞表面抗原,因此有可能比 CAR-T 细胞识别更多的靶抗原,为治疗实体瘤提供了巨大的希望。人们对 TCR-T 细胞治疗实体瘤的应用越来越感兴趣,目前全球正在进行 56 项临床试验以确认其有效性。在这篇综述中,我们总结了 TCR-T 细胞治疗的临床研究的最新进展,描述了 TCR-T 细胞的制备和鉴定策略,重点介绍了抗原选择、TCR 分离以及进一步增强过继转移细胞效力的方法。