嵌合抗原受体 T 细胞疗法中的抗原逃逸：机制与克服策略。

Antigen escape in CAR-T cell therapy: Mechanisms and overcoming strategies.

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei 430030, China; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.

出版信息

Biomed Pharmacother. 2024 Sep;178:117252. doi: 10.1016/j.biopha.2024.117252. Epub 2024 Aug 3.

DOI:10.1016/j.biopha.2024.117252

PMID:39098176

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy has shown promise in treating hematological malignancies and certain solid tumors. However, its efficacy is often hindered by negative relapses resulting from antigen escape. This review firstly elucidates the mechanisms underlying antigen escape during CAR-T cell therapy, including the enrichment of pre-existing target-negative tumor clones, antigen gene mutations or alternative splicing, deficits in antigen processing, antigen redistribution, lineage switch, epitope masking, and trogocytosis-mediated antigen loss. Furthermore, we summarize various strategies to overcome antigen escape, evaluate their advantages and limitations, and propose future research directions. Thus, we aim to provide valuable insights to enhance the effectiveness of CAR-T cell therapy.

摘要

嵌合抗原受体 T（CAR-T）细胞疗法在治疗血液系统恶性肿瘤和某些实体瘤方面显示出巨大的潜力。然而，其疗效常常受到抗原逃逸导致的阴性复发的阻碍。本综述首先阐明了 CAR-T 细胞治疗过程中抗原逃逸的机制，包括预先存在的靶阴性肿瘤克隆的富集、抗原基因突变或选择性剪接、抗原加工缺陷、抗原重新分布、谱系转换、表位掩蔽以及 trogocytosis 介导的抗原丢失。此外，我们总结了克服抗原逃逸的各种策略，评估了它们的优缺点，并提出了未来的研究方向。因此，我们旨在提供有价值的见解，以提高 CAR-T 细胞治疗的效果。