CAR-T细胞治疗产品及其非临床评价研究概述

Non-clinical evaluation of CAR-T cell therapy products

嵌合抗原受体T细胞(CAR-T细胞)是近年来在肿瘤免疫治疗领域最具有前景的治疗方法之一,在临床试验中取得了显著疗效,但随着其大面积推广,其安全性同样不容忽视。根据CAR-T细胞的毒性作用机制,主要存在肿瘤靶向、脱靶效应和脱靶肿瘤外的安全性问题。由于CAR-T细胞制备的特殊性,需要针对CAR-T细胞的不同靶点特点和适应证等多方面因素综合考虑,设计合理的非临床实验方案,选择合适的动物模型评价其有效性和安全性,为临床试验的顺利开展提供依据。本文将对CAR-T细胞的结构、原理及临床应用和非临床评价做简要介绍,为CAR-T的成功研发提供技术支撑。

Chimeric antigen receptor-T(CAR-T) cells are a promising treatment for tumor immunotherapy in recent years. It has achieved fairly good results in clinical trials. However, with large area promotion, its safety cannot be ignored. According to the toxic mechanism of CAR-T cells, the main safety problems lie in on-target, on tumor, on-target, off tumor and off-target, off tumor. Due to the particularity of CAR-T cell preparation, it is important to comprehensively consider the different target characteristics and indications of CAR-T cells, design a reasonable experimental scheme, select appropriate animal models, and evaluate its safety and effectiveness. This article briefly introduced the structure, principle, clinical application and non-clinical evaluation of CAR-T cells, and provided technical support for the successful development of CAR-T.