CAR-T细胞体内外扩增方法的优化策略  

Optimization strategies for the amplification of CAR-T cells in vitro and in vivo

作　　者：潘心怡 任政乾 王欣玥 王婷婷[1] PAN Xinyi;REN Zhengqian;WANG Xinyue;WANG Tingting(Medical School of Nanjing University,Nanjing 210000,Jiangsu,China)

机构地区：[1]南京大学医学院,江苏南京210000

出　　处：《中国肿瘤生物治疗杂志》2024年第7期647-654,共8页Chinese Journal of Cancer Biotherapy

基　　金：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)。

摘　　要：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.

关 键 词：肿瘤 实体瘤 免疫治疗 CAR-T细胞疗法 特异性扩增 

分 类 号：R392.12[医药卫生—免疫学] R730.51[医药卫生—基础医学]