Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity
Abstract Although tumor‐specific neoantigen‐based cancer vaccines hold tremendous potential, it still faces low cross‐presentation associated with severe degradation via endocytosis pathway. Herein, a thiolated nano‐vaccine allowing direct cytosolic delivery of neoantigen and Toll like receptor 9 ag...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-03-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202003504 |
| _version_ | 1818848350153211904 |
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| author | Da Zhang Ziguo Lin Ming Wu Zhixiong Cai Youshi Zheng Lei He Zhenli Li Jie Zhou Liqin Sun Geng Chen Yongyi Zeng Juan Li Jingfeng Liu Huanghao Yang Xiaolong Liu |
| author_facet | Da Zhang Ziguo Lin Ming Wu Zhixiong Cai Youshi Zheng Lei He Zhenli Li Jie Zhou Liqin Sun Geng Chen Yongyi Zeng Juan Li Jingfeng Liu Huanghao Yang Xiaolong Liu |
| author_sort | Da Zhang |
| collection | DOAJ |
| description | Abstract Although tumor‐specific neoantigen‐based cancer vaccines hold tremendous potential, it still faces low cross‐presentation associated with severe degradation via endocytosis pathway. Herein, a thiolated nano‐vaccine allowing direct cytosolic delivery of neoantigen and Toll like receptor 9 agonist CpG‐ODN is developed. This approach is capable of bypassing the endo‐/lysosome degradation, increasing uptake and local concentration of neoantigen and CpG‐ODN to activate antigen‐presenting cells, significantly strengthening the anti‐cancer T‐cell immunity. In vivo immunization with thiolated nano‐vaccine enhanced the lymph organ homing and promoted the antigen presentation on dendritic cells, effectively inhibited tumor growth, and significantly prolonged the survival of H22‐bearing mice. Strikingly, further combination of the thiolated nano‐vaccine with anti‐programmed cell death protein‐1 antibody (αPD‐1) could efficiently reverse immunosuppression and enhance response rate of tumors, which led to enhanced tumor elimination, complete prevention of tumor re‐challenge, and long‐term survival above 150 d. Collectively, a versatile methodology to design cancer vaccines for strengthening anti‐cancer T‐cell immunity in solid tumors is presented, which could be further remarkably enhanced by combining with immune checkpoint inhibitors. |
| first_indexed | 2024-12-19T06:15:56Z |
| format | Article |
| id | doaj.art-5b9ab3857f8641268dcfad7da7135885 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-19T06:15:56Z |
| publishDate | 2021-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-5b9ab3857f8641268dcfad7da71358852022-12-21T20:32:52ZengWileyAdvanced Science2198-38442021-03-0186n/an/a10.1002/advs.202003504Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell ImmunityDa Zhang0Ziguo Lin1Ming Wu2Zhixiong Cai3Youshi Zheng4Lei He5Zhenli Li6Jie Zhou7Liqin Sun8Geng Chen9Yongyi Zeng10Juan Li11Jingfeng Liu12Huanghao Yang13Xiaolong Liu14The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe Key Lab of Analysis and Detection Technology for Food Safety of the MOE, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry Fuzhou University Fuzhou 350002 P. R. ChinaThe Key Lab of Analysis and Detection Technology for Food Safety of the MOE, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry Fuzhou University Fuzhou 350002 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe Key Lab of Analysis and Detection Technology for Food Safety of the MOE, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry Fuzhou University Fuzhou 350002 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaThe Key Lab of Analysis and Detection Technology for Food Safety of the MOE, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry Fuzhou University Fuzhou 350002 P. R. ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. ChinaAbstract Although tumor‐specific neoantigen‐based cancer vaccines hold tremendous potential, it still faces low cross‐presentation associated with severe degradation via endocytosis pathway. Herein, a thiolated nano‐vaccine allowing direct cytosolic delivery of neoantigen and Toll like receptor 9 agonist CpG‐ODN is developed. This approach is capable of bypassing the endo‐/lysosome degradation, increasing uptake and local concentration of neoantigen and CpG‐ODN to activate antigen‐presenting cells, significantly strengthening the anti‐cancer T‐cell immunity. In vivo immunization with thiolated nano‐vaccine enhanced the lymph organ homing and promoted the antigen presentation on dendritic cells, effectively inhibited tumor growth, and significantly prolonged the survival of H22‐bearing mice. Strikingly, further combination of the thiolated nano‐vaccine with anti‐programmed cell death protein‐1 antibody (αPD‐1) could efficiently reverse immunosuppression and enhance response rate of tumors, which led to enhanced tumor elimination, complete prevention of tumor re‐challenge, and long‐term survival above 150 d. Collectively, a versatile methodology to design cancer vaccines for strengthening anti‐cancer T‐cell immunity in solid tumors is presented, which could be further remarkably enhanced by combining with immune checkpoint inhibitors.https://doi.org/10.1002/advs.202003504cytosolic deliveryimmune checkpointneoantigenT‐cells immunitythiolated nano‐vaccine |
| spellingShingle | Da Zhang Ziguo Lin Ming Wu Zhixiong Cai Youshi Zheng Lei He Zhenli Li Jie Zhou Liqin Sun Geng Chen Yongyi Zeng Juan Li Jingfeng Liu Huanghao Yang Xiaolong Liu Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity Advanced Science cytosolic delivery immune checkpoint neoantigen T‐cells immunity thiolated nano‐vaccine |
| title | Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity |
| title_full | Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity |
| title_fullStr | Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity |
| title_full_unstemmed | Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity |
| title_short | Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity |
| title_sort | cytosolic delivery of thiolated neoantigen nano vaccine combined with immune checkpoint blockade to boost anti cancer t cell immunity |
| topic | cytosolic delivery immune checkpoint neoantigen T‐cells immunity thiolated nano‐vaccine |
| url | https://doi.org/10.1002/advs.202003504 |
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