抗原改造联合纳米肿瘤疫苗用以克服肿瘤新抗原短缺及在多种肿瘤类型上激起强效抗肿瘤免疫反应  

Hit-and-run vaccine system that overcomes limited neoantigen epitopes for efficient broad antitumor response

作　　者：陈宏宇 黄子超 李佳玄 董思 徐玉笛 马胜 赵佳雨 刘丽萍 孙天盟 宋万通 陈学思 Hongyu Chen;Zichao Huang;Jiaxuan Li;Si Dong;Yudi Xu;Sheng Ma;Jiayu Zhao;Liping Liu;Tianmeng Sun;Wantong Song;Xuesi Chen(School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230026,China;Key laboratory of Polymer Ecomaterials,Changchun Institue of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China;Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education,Institute of Immunology,The First Hospital,Jilin University,Changchun 130021,China;Jilin Biomedical Polymers Engineering Laboratory,Changchun 130022,China)

机构地区：[1]School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230026,China [2]Key laboratory of Polymer Ecomaterials,Changchun Institue of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China [3]Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education,Institute of Immunology,The First Hospital,Jilin University,Changchun 130021,China [4]Jilin Biomedical Polymers Engineering Laboratory,Changchun 130022,China

出　　处：《Science Bulletin》2024年第7期922-932,共11页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (22222509, 52025035, 52103194, and 22105199);The Ministry of Science and Technology of China (2022YFE0110200);Bureau of International Cooperation Chinese Academy of Sciences (121522KYSB20200029);Jilin Province Science and Technology Development Plan (YDZJ202101ZYTS131, 20220402037GH, and 20210508049RQ);Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers (20210504001GH);The Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232)。

摘　　要：Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.

关 键 词：Cancer immunotherapy Cancer vaccine NEOANTIGEN NANOCARRIER Poly(2-oxazoline)s 

分 类 号：R730.51[医药卫生—肿瘤]