A Universal Strategy of Anti‐Tumor mRNA Vaccine by Harnessing “Off‐the‐Shelf” Immunity
Abstract Personalized neoantigen cancer mRNA vaccines are promising candidates for precision medicine. However, the difficulty of identifying neoantigens heavily hinders their broad applicability. This study developed a universal strategy of anti‐tumor mRNA vaccine by harnessing “off‐the‐shelf” immu...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202401287 |
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| author | Jiayan Fu Shuangqi Wu Nengcheng Bao Lili Wu Huiru Qu Zhechao Wang Haiyang Dong Jian Wu Yongfeng Jin |
| author_facet | Jiayan Fu Shuangqi Wu Nengcheng Bao Lili Wu Huiru Qu Zhechao Wang Haiyang Dong Jian Wu Yongfeng Jin |
| author_sort | Jiayan Fu |
| collection | DOAJ |
| description | Abstract Personalized neoantigen cancer mRNA vaccines are promising candidates for precision medicine. However, the difficulty of identifying neoantigens heavily hinders their broad applicability. This study developed a universal strategy of anti‐tumor mRNA vaccine by harnessing “off‐the‐shelf” immunity to known antigens. First, the model antigen ovalbumin (OVA) is used for mRNA vaccine design. In vitro test indicated that this mRNA vaccine reprogrammed tumor cells that can be recognized and killed by OVA‐specific cytotoxic T lymphocytes (CTLs). In situ mRNA vaccine notably inhibited tumor growth across three subcutaneous solid tumor models in mice. Further single‐cell sequencing analyses revealed that mRNA vaccination act to reshape the immunosuppressive tumor microenvironment (TME) toward more proinflammatory characteristics. Strikingly, this framework of mRNA‐based strategy can be applied to two clinical pathogen antigens, hepatitis B surface antigen (HBsAg), and SARS‐CoV‐2 spike receptor‐binding domain (SRBD). Interestingly, the mRNA‐based strategy largely recapitulated the scenario of spontaneous cancer regression following pathogen infection or vaccination. Collectively, this study provides not only proof of concept for universal anti‐tumor mRNA therapy, but also mechanistic insights in echoing the long‐standing puzzle of spontaneous cancer regression. |
| format | Article |
| id | doaj-art-3f9ca093ff6e4d6fb6c41b2b82d1e903 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-3f9ca093ff6e4d6fb6c41b2b82d1e9032025-08-20T03:49:36ZengWileyAdvanced Science2198-38442025-02-01128n/an/a10.1002/advs.202401287A Universal Strategy of Anti‐Tumor mRNA Vaccine by Harnessing “Off‐the‐Shelf” ImmunityJiayan Fu0Shuangqi Wu1Nengcheng Bao2Lili Wu3Huiru Qu4Zhechao Wang5Haiyang Dong6Jian Wu7Yongfeng Jin8National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University Hangzhou Zhejiang 310058 ChinaNational Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University Hangzhou Zhejiang 310058 ChinaNational Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University Hangzhou Zhejiang 310058 ChinaNational Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University Hangzhou Zhejiang 310058 ChinaNational Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University Hangzhou Zhejiang 310058 ChinaNational Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University Hangzhou Zhejiang 310058 ChinaNational Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310006 ChinaNational Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University Hangzhou Zhejiang 310058 ChinaAbstract Personalized neoantigen cancer mRNA vaccines are promising candidates for precision medicine. However, the difficulty of identifying neoantigens heavily hinders their broad applicability. This study developed a universal strategy of anti‐tumor mRNA vaccine by harnessing “off‐the‐shelf” immunity to known antigens. First, the model antigen ovalbumin (OVA) is used for mRNA vaccine design. In vitro test indicated that this mRNA vaccine reprogrammed tumor cells that can be recognized and killed by OVA‐specific cytotoxic T lymphocytes (CTLs). In situ mRNA vaccine notably inhibited tumor growth across three subcutaneous solid tumor models in mice. Further single‐cell sequencing analyses revealed that mRNA vaccination act to reshape the immunosuppressive tumor microenvironment (TME) toward more proinflammatory characteristics. Strikingly, this framework of mRNA‐based strategy can be applied to two clinical pathogen antigens, hepatitis B surface antigen (HBsAg), and SARS‐CoV‐2 spike receptor‐binding domain (SRBD). Interestingly, the mRNA‐based strategy largely recapitulated the scenario of spontaneous cancer regression following pathogen infection or vaccination. Collectively, this study provides not only proof of concept for universal anti‐tumor mRNA therapy, but also mechanistic insights in echoing the long‐standing puzzle of spontaneous cancer regression.https://doi.org/10.1002/advs.202401287anti‐tumormRNA vaccineproof of conceptspontaneous cancer regressionuniversal strategy |
| spellingShingle | Jiayan Fu Shuangqi Wu Nengcheng Bao Lili Wu Huiru Qu Zhechao Wang Haiyang Dong Jian Wu Yongfeng Jin A Universal Strategy of Anti‐Tumor mRNA Vaccine by Harnessing “Off‐the‐Shelf” Immunity Advanced Science anti‐tumor mRNA vaccine proof of concept spontaneous cancer regression universal strategy |
| title | A Universal Strategy of Anti‐Tumor mRNA Vaccine by Harnessing “Off‐the‐Shelf” Immunity |
| title_full | A Universal Strategy of Anti‐Tumor mRNA Vaccine by Harnessing “Off‐the‐Shelf” Immunity |
| title_fullStr | A Universal Strategy of Anti‐Tumor mRNA Vaccine by Harnessing “Off‐the‐Shelf” Immunity |
| title_full_unstemmed | A Universal Strategy of Anti‐Tumor mRNA Vaccine by Harnessing “Off‐the‐Shelf” Immunity |
| title_short | A Universal Strategy of Anti‐Tumor mRNA Vaccine by Harnessing “Off‐the‐Shelf” Immunity |
| title_sort | universal strategy of anti tumor mrna vaccine by harnessing off the shelf immunity |
| topic | anti‐tumor mRNA vaccine proof of concept spontaneous cancer regression universal strategy |
| url | https://doi.org/10.1002/advs.202401287 |
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