Overcoming tumor antigen heterogeneity in CAR-T cell therapy for malignant mesothelioma(MM)  

作　　者：Reena R.D'Souza Paraskevi Dimou Reyisa Bughda Elizabeth Hawkins Clara Leboreiro Babe Astero Klampatsa 

机构地区：[1]Division of Cancer Therapeutics,The Institute of Cancer Research,London SM25NG,UK [2]Division of Radiotherapy and Imaging,The Institute of Cancer Research,London SM25NG,UK

出　　处：《Journal of Cancer Metastasis and Treatment》2022年第1期302-316,共15页癌症转移与治疗（英文版）

摘　　要：Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic response.The role of immunotherapy in MM is now well established and therapeutic options,such as checkpoint inhibitors,are increasingly being approved.Chimeric antigen receptor(CAR)-T cell therapy is successfully implemented in several hematologic cancers,but currently has inadequate effect in solid tumors,owing to several limitations,such as trafficking and infiltration,limited T cell persistence and exhaustion,the immunosuppressive TME and tumor antigen heterogeneity.The lack of uniform and universal expression of tumor-associated antigens(TAAs)on tumor cells,as well as TAA heterogeneity following tumor editing post-therapy,are issues of significant importance to CAR-T cell and associated antigen-targeting therapies.Our review discusses the concept of tumor antigen heterogeneity in MM,the consequences for CAR-T cell therapies and the strategies to overcome it.

关 键 词：Antigen heterogeneity chimeric antigen receptor(CAR)T cells MESOTHELIOMA tumor-associated antigens(TAAs) bystander effect epitope spreading tumor microenvironment 

分 类 号：R734.3[医药卫生—肿瘤]