ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Int Rev Immunol. 2022;41(6):625-637. doi: 10.1080/08830185.2022.2102619. Epub 2022 Jul 20.
Since B7-H3 is overexpressed or amplified in many types of solid tumors with a restricted expression in the normal tissues, it has been an emerging immunotherapeutic target for solid tumors. This review will focus on the structural designs of developing chimeric antigen receptors (CARs) targeting B7-H3. The expression, receptor, and function of the B7-H3, as well as a short overview of B7-H3-targeted monoclonal antibody therapy, are discussed. Finally, a detailed summary of B7-H3 redirected CAR-T and CAR-NK cell approaches utilized in preclinical models and currently ongoing or completed clinical trials are presented. It has been demonstrated that B7-H3-targeted CAR-based cell therapies were safe in initial trials, but their efficacy was limited. Employing the local delivery routes, the introduction of novel modifications promoting CAR-T persistence, and combined treatment with other standard therapies could improve the efficacy of B7-H3-targeted CAR-T cell therapy against solid tumors.
由于 B7-H3 在许多类型的实体瘤中过表达或扩增,而在正常组织中表达受限,因此它已成为实体瘤新兴的免疫治疗靶点。本综述将重点介绍针对 B7-H3 的嵌合抗原受体 (CAR) 的结构设计。讨论了 B7-H3 的表达、受体和功能,以及 B7-H3 靶向单克隆抗体治疗的简要概述。最后,详细总结了在临床前模型中使用的 B7-H3 重定向 CAR-T 和 CAR-NK 细胞方法,以及目前正在进行或已完成的临床试验。已证明 B7-H3 靶向 CAR 为基础的细胞疗法在初步试验中是安全的,但疗效有限。采用局部给药途径、引入促进 CAR-T 持续存在的新型修饰以及与其他标准疗法联合治疗,可提高 B7-H3 靶向 CAR-T 细胞疗法治疗实体瘤的疗效。