嵌合抗原受体T细胞免疫原性的研究现状

Research status on immunogenicity of chimeric antigen receptor T cell immunotherapy

嵌合抗原受体T细胞(CAR-T)免疫疗法是近年来极具发展前景的免疫过继疗法之一。CAR-T免疫原性与抗嵌合抗原受体(CAR)特异性免疫反应可导致CAR-T体内扩增能力下降及存活时间缩短,从而导致原发疾病复发,限制其临床应用。CAR-T免疫原性的影响因素众多,其中研究最为广泛的是鼠源性单链可变区(scFv)构建CAR结构所产生的免疫原性。目前已有多种降低CAR-T免疫原性,从而延长CAR-T体内存活时间,增强疗效的方法,如解决CAR结构非人源化问题等。为了深入探讨影响CAR-T免疫疗法疗效及安全性的相关因素,笔者拟就CAR-T的免疫原性、其产生的免疫反应进行阐述,同时探讨可降低CAR-T免疫原性的相关措施,以期进一步增加CAR-T免疫疗法的临床应用。

Chimeric antigen receptor T cell(CAR-T)immunotherapy is one of the most promising immunological adoptive therapies in recent years.Immunogenicity of CAR-T and anti-chimeric antigen receptor(CAR)specific immune response limit the expansion of CAR-T in vivo and shorten the persistence of CAR-T,which cause the recurrence of primary disease and limit its clinical application.There are many factors affecting immunogenicity of CAR-T,among which the most widely studied,is the murine single-chain variable region(scFv)of CAR structure.There are currently a variety of strategies to reduce the immunogenicity of CAR-T,thus extending the persistence of CAR-T in vivo and enhancing the efficacy therefore,such as solving the problem of non-humanized CAR structure.In order to investigate the factors affecting the efficacy and safety of CAR-T immunotherapy,this article intends to elaborate on the immunogenicity of CAR-T,immune response it generates,as well as to discuss measures that can reduce the immunogenicity of CAR-T,to further increase the clinical application of CAR-T immunotherapy.