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实体瘤基因工程 T 细胞受体修饰的淋巴细胞的癌症免疫疗法。

Cancer immunotherapy with lymphocytes genetically engineered with T cell receptors for solid cancers.

机构信息

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.

出版信息

Immunol Lett. 2019 Dec;216:51-62. doi: 10.1016/j.imlet.2019.10.002. Epub 2019 Oct 6.

Abstract

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.

摘要

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。

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