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

Hongyu Chen ¹Zichao Huang ¹Jiaxuan Li ²Si Dong ³Yudi Xu ³Sheng Ma ⁴Jiayu Zhao ¹Liping Liu ¹Tianmeng Sun ²Wantong Song ⁵Xuesi Chen⁵

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作者信息

1. 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
2. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education,Institute of Immunology,The First Hospital,Jilin University,Changchun 130021,China
3. Key laboratory of Polymer Ecomaterials,Changchun Institue of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China
4. Key laboratory of Polymer Ecomaterials,Changchun Institue of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China;Jilin Biomedical Polymers Engineering Laboratory,Changchun 130022,China
5. 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;Jilin Biomedical Polymers Engineering Laboratory,Changchun 130022,China
折叠

Abstract

Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer thera-pies.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 strat-egy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decora-tion with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx)conjugated with OVA257-264 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 OVA257-264 peptides to elicit OVA-specific T cell responses was designed.In com-bination 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 vac-cine strategy against tumors with a low tumor mutation burden.

Key words

Cancer immunotherapy/Cancer vaccine/Neoantigen/Nanocarrier/Poly(2-oxazoline)s

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基金项目

National Natural Science Foundation of China(22222509)

National Natural Science Foundation of China(52025035)

National Natural Science Foundation of China(52103194)

National Natural Science Foundation of China(22105199)

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)

Jilin Province Science and Technology Development Plan(20220402037GH)

Jilin Province Science and Technology Development Plan(20210508049RQ)

Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(20210504001GH)

Youth Innovation Promotion Association of Chinese Academy of Sciences(2020232)

出版年

2024

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

参考文献量46

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