嵌合抗原受体基因修饰T（CAR-T）细胞免疫治疗被认为是最有前景的肿瘤治疗方法之一，效应CAR-T细胞的数量是 决定CAR-T细胞疗法治疗效果的关键因素。CAR-T细胞的体外扩增耗时耗力，回输体内后，CAR-T细胞大量耗竭且难以浸润实 体瘤，导致能有效抑制实体瘤的CAR-T细胞数量大幅下降。目前，CAR-T细胞的扩增方法在提高扩增特异性和治疗安全性等方 面均存在问题，为CAR-T细胞疗法的临床转化造成困难。近年来，新型免疫激动剂及其下游信号的发现为CAR-T细胞扩增方案 提供了更多选择，免疫激动剂给药方式的更新迭代进一步提高了其在体内扩增CAR-T细胞的安全性。本文分析了目前扩增CAR-T细 胞面临的挑战，系统阐述了近年来在体内外扩增CAR-T细胞的新策略，为CAR-T细胞疗法的疗效和产能优化提供了新思路。

Chimeric antigen receptor gene-modified T (CAR-T) cell immunotherapy is considered as one of the most promising tumor treatments. The number of effector CAR-T cells is a key factor in determining the therapeutic effect of CAR-T cell therapy. The expansion of CAR-T cells in vitro is time and energy-consuming. After transfusion, it’s difficult for CAR-T cells to infiltrate into solid tumors, resulting in a significant decrease in the number of CAR-T cells that can effectively inhibit solid tumors. Currently, the amplification of CAR-T cells has problems in enhancing amplification specificity and treatment safety, which hinders the clinical transformation of CAR-T cell therapy. In recent years, achievements in new immunity agonist and their downstream signals have provided more options for CAR-T amplification, and the novel administration methods of immunity agonist have further improved the safety of CAR-T amplification in vivo. This review analyzes the current challenges in CAR-T cell amplification, and systematically expounds the new strategies of CAR-T cell amplification in vitro and in vivo in recent years, providing new thoughts for the efficacy and capacity optimization of CAR-T cell therapy.

中国博士后科学基金面上资助项目（No. 2023M741629）；国家自然科学基金面上项目（No. 82273011, No. 82072648）