An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy

作者全名："Chen, Xiangyu; Zhao, Jing; Yue, Shuai; Li, Ziyu; Duan, Xiang; Lin, Yao; Yang, Yang; He, Junjian; Gao, Leiqiong; Pan, Zhiwei; Yang, Xiaofan; Su, Xingxing; Huang, Min; Li, Xiao; Zhao, Ye; Zhang, Xuehui; Li, Zhirong; Hu, Li; Tang, Jianfang; Hao, Yaxing; Tian, Qin; Wang, Yifei; Xu, Lifan; Huang, Qizhao; Cao, Yingjiao; Chen, Yaokai; Zhu, Bo; Li, Yan; Bai, Fan; Zhang, Guozhong; Ye, Lilin"

作者地址："[Chen, Xiangyu; Wang, Yifei; Huang, Qizhao] Chongqing Med Univ, Inst Immunol Innovat & Translat, Chongqing, Peoples R China; [Chen, Xiangyu; Ye, Lilin] Changping Lab, Beijing, Peoples R China; [Zhao, Jing; Huang, Min; Li, Xiao; Zhao, Ye; Zhang, Xuehui; Zhang, Guozhong] China Agr Univ, Coll Vet Med, Key Lab Anim Epidemiol, Minist Agr, Beijing, Peoples R China; [Yue, Shuai; Lin, Yao; He, Junjian; Gao, Leiqiong; Pan, Zhiwei; Li, Zhirong; Hu, Li; Tang, Jianfang; Hao, Yaxing; Xu, Lifan; Ye, Lilin] Third Mil Med Univ, Inst Immunol, Chongqing, Peoples R China; [Yue, Shuai] Third Mil Med Univ, Daping Hosp, Canc Ctr, Chongqing, Peoples R China; [Yue, Shuai] Third Mil Med Univ, Army Med Ctr PLA, Chongqing, Peoples R China; [Li, Ziyu; Bai, Fan] Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Sch Life Sci, Beijing, Peoples R China; [Li, Ziyu; Bai, Fan] Peking Univ, Beijing Adv Innovat Ctr Genom, Beijing, Peoples R China; [Duan, Xiang; Li, Yan] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Engn Res Ctr Prot & Peptide Med, Natl Resource Ctr Mutant Mice,MOE,Key Lab Model An, Nanjing, Peoples R China; [Yang, Yang; Cao, Yingjiao] Southern Med Univ, Sch Lab Med & Biotechnol, Guangdong Prov Key Lab Immune Regulat & Immunother, Guangzhou, Peoples R China; [Yang, Xiaofan; Tian, Qin] Southern Med Univ, Dermatol Hosp, Guangzhou, Peoples R China; [Su, Xingxing] Third Mil Med Univ, Southwest Hosp, Dept Hepatobiliary Surg, Chongqing, Peoples R China; [Chen, Yaokai] Chongqing Publ Hlth Med Ctr, Dept Infect Dis, Chongqing, Peoples R China; [Zhu, Bo] Third Mil Med Univ, Xinqiao Hosp, Inst Canc, Chongqing, Peoples R China"

通信作者："Ye, LL (通讯作者)，Changping Lab, Beijing, Peoples R China.; Zhang, GZ (通讯作者)，China Agr Univ, Coll Vet Med, Key Lab Anim Epidemiol, Minist Agr, Beijing, Peoples R China.; Ye, LL (通讯作者)，Third Mil Med Univ, Inst Immunol, Chongqing, Peoples R China.; Bai, F (通讯作者)，Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Sch Life Sci, Beijing, Peoples R China.; Bai, F (通讯作者)，Peking Univ, Beijing Adv Innovat Ctr Genom, Beijing, Peoples R China.; Li, Y (通讯作者)，Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Engn Res Ctr Prot & Peptide Med, Natl Resource Ctr Mutant Mice,MOE,Key Lab Model An, Nanjing, Peoples R China."

来源：NATURE CANCER

ESI学科分类：　

WOS号：WOS:001201343900001

JCR分区：Q1

影响因子：22.7

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in the tumor microenvironment (TME), leading to inefficacious immunotherapies in most patients with cancer. By contrast, emerging evidence suggested that tumor-irrelevant bystander T (TBYS) cells are abundant and preserve functional memory properties in the TME. To leverage TBYS cells in the TME to eliminate tumor cells, we engineered oncolytic virus (OV) encoding TBYS epitopes (OV-BYTE) to redirect the antigen specificity of tumor cells to pre-existing TBYS cells, leading to effective tumor inhibition in multiple preclinical models. Mechanistically, OV-BYTE induced epitope spreading of tumor antigens to elicit more diverse tumor-specific T cell responses. Remarkably, the OV-BYTE strategy targeting human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory efficiently inhibited tumor progression in a human tumor cell-derived xenograft model, providing important insights into the improvement of cancer immunotherapies in a large population with a history of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination. Ye and colleagues show that an oncolytic virus that delivers tumor-irrelevant bystander T cell epitopes to tumor cells can exploit the abundant population of bystander T cells in the tumor for anti-tumor immunity and potentiate cancer immunotherapy."

基金机构："National Natural Science Foundation of China (National Science Foundation of China) [31825011]; National Natural Science Fund for Distinguished Young Scholars [2021YFC2300502]; National Science and Technology Major Project [32070942, 32122035]; National Natural Science Foundation of China [BX20230449]; China National Postdoctoral Program for Innovative Talents [2019YFA0802900]; National Key Research and Development Program of China"

基金资助正文："This study was supported by grants from the National Natural Science Fund for Distinguished Young Scholars (no. 31825011 to L.Y.), the National Science and Technology Major Project (no. 2021YFC2300602 to L.Y.), the National Science and Technology Major Project (no. 2021YFC2300502 to L.Y.), the National Natural Science Foundation of China (no. 32300785 to X.C.), the China National Postdoctoral Program for Innovative Talents (no. BX20230449 to X.C.), the 2115 Talent Development Program of China Agricultural University (G.Z.), the National Key Research and Development Program of China (no. 2019YFA0802900 to Y. Li) and the National Natural Science Foundation of China (no. 32070942 to Y. Li, no. 32122035 to Y. Li)."