Neoantigen vaccine and neoantigen-specific cell adoptive transfer therapy in solid tumors:Challenges and future directions  

作　　者：Yanwei Shen Lu Yu Xiaoli Xu Shaojun Yu Zhuo Yu 

机构地区：[1]Shanghai Jianshan Medical Tech Co Ltd,Shanghai,China [2]Department of Surgery,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [3]Department of Medical Oncology,Beijing Tsinghua Changgung Hospital,School of Clinical Medicine,Tsinghua University,Beijing,China

出　　处：《Cancer Innovation》2022年第2期168-182,共15页肿瘤创新（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Numbers:81972444,82172566。

摘　　要：The phenomenon of tumor hierarchy and genetic instability can be explained by the“two-hits theory”and results in the occurrence of many somatic mutations.The expression of nonsynonymous mutations results in the production of mutant proteins from tumor cells,namely tumor-specific antigens called neoantigens.Because neoantigens do not exist in healthy cells,they have the potential to stimulate antitumor immune responses by CD4+and CD8+T-cell activation without jeopardizing normal tissues.Immunotherapy has reshaped the cancer treatment paradigm in recent decades with the introduction of immune-checkpoint blockade therapy and transgenic Tcell receptor/chimeric antigen receptor T cells.However,these strategies performed poorly in solid tumors because of the obstacles of the immunosuppressive microenvironment caused by regulatory T cells and other suppressor cells.Therefore,other immunotherapeutic strategies are under development,such as personalized vaccines,to trigger de novo T-cell responses against neoantigens and lead to the amplification of tumorspecific T-cell subclones.Neoantigen epitope prediction algorithms have enabled the detection of neoantigens and the creation of tailored neoantigen vaccines as a result of the fast development of next-generation sequencing and cancer bioinformatics.Here we provide an overview of the current neoantigen cancer vaccines and adoptive T-cell transfer therapy with neoantigen-specific lymphocytes.We also discuss the challenges in developing neoantigentargeted immunotherapeutic strategies for cancer.

关 键 词：NEOANTIGEN cancer vaccine IMMUNOTHERAPY tumor microenvironment HETEROGENEITY precision medicine 

分 类 号：R73-37[医药卫生—肿瘤]