肿瘤免疫疗法中细胞来源对治疗效果的影响  

The impact of immune cells selection on the therapeutic efficacy of CAR-T cell therapy

作　　者：齐文昕 张伟龙 景红梅[1] QiWenxin;Zhang Weilong;Jing Hongmei(Department of Hematology,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第三医院血液科,北京100191

出　　处：《中华血液学杂志》2024年第7期699-704,共6页Chinese Journal of Hematology

摘　　要：从免疫细胞层面总结了各种新型嵌合抗原受体T细胞(CAR-T细胞)疗法,健康年轻受试者的T细胞、干性记忆样T细胞、人体诱导多能干细胞、脐带血T细胞来源的CAR-T细胞疗法可增强肿瘤杀伤效应。从通用型CAR细胞方面,病毒特异性T细胞、γδT细胞、iNKT细胞、巨噬细胞等能有效减轻移植物抗宿主病反应。此外,增强去白细胞过程中单核细胞的清除、保持CD4^(+)/CD8^(+)T细胞均衡比例等策略也是增强CAR-T细胞扩增及杀伤效力的方法。细胞耗竭标志物高表达的T细胞对CAR-T细胞的转导、扩增及发挥杀伤效力等会产生负向影响,使用免疫检查点阻断剂等方式抑制T细胞耗竭能提高CAR-T细胞作用效应。Here we summarized novel Chimeric antigen receptor T-cell immunotherapy(CAR-T)based on the immune material aspect.Young healthy donor T cells,stem cell-like memory T cells,human induced pluripotent stem cells and umbilical cord blood T cells are all potential candidates to enhance CAR-T cell therapy depending on their anti-tumor efficacy.Besides,due to less restricted major histocompatibility complex(MHC)mismatch effect,viral specific T cells,γδT cells,invariant natural killer T cells and macrophages also become idealized T cell sources in terms of Universal CAR-T(UCAR-T)cell therapeutics.In addition,studies demonstrated that more balanced CD4^(+)/CD8^(+)T cell ratio and eliminating monocytes during leukapheresis have a positive influence on CAR-T cell functioning,whereas T cells with higher exhaustion markers expression hampers anti-tumor ability of CAR-T cells after infusion.To avoid application of such T cells or mitigate the impact using immune checkpoint inhibitors is of great importance.

关 键 词：移植物抗宿主病 肿瘤免疫疗法 诱导多能干细胞 特异性T细胞 去白细胞 脐带血 巨噬细胞 ΓΔT细胞 

分 类 号：R730.51[医药卫生—肿瘤]