Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system
Abstract Embryonic stem cell (ESC)-derived epitopes can act as therapeutic tumor vaccines against different types of tumors Jin (Adv Healthc Mater 2023). However, these epitopes have poor immunogenicity and stimulate insufficient CD8+ T cell responses, which motivated us to develop a new method to d...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-023-02273-8 |
| _version_ | 1827388201959948288 |
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| author | Meiling Jin Da Huo Jingjing Sun Jingchu Hu Shuzhen Liu Mingshuo Zhan Bao-zhong Zhang Jian-Dong Huang |
| author_facet | Meiling Jin Da Huo Jingjing Sun Jingchu Hu Shuzhen Liu Mingshuo Zhan Bao-zhong Zhang Jian-Dong Huang |
| author_sort | Meiling Jin |
| collection | DOAJ |
| description | Abstract Embryonic stem cell (ESC)-derived epitopes can act as therapeutic tumor vaccines against different types of tumors Jin (Adv Healthc Mater 2023). However, these epitopes have poor immunogenicity and stimulate insufficient CD8+ T cell responses, which motivated us to develop a new method to deliver and enhance their effectiveness. Bacterial outer membrane vesicles (OMVs) can serve as immunoadjuvants and act as a delivery vector for tumor antigens. In the current study, we engineered a new OMV platform for the co-delivery of ESC-derived tumor antigens and immune checkpoint inhibitors (PD-L1 antibody). An engineered Staphylococcal Protein A (SpA) was created to non-specifically bind to anti-PD-L1 antibody. SpyCatcher (SpC) and SpA were fused into the cell outer membrane protein OmpA to capture SpyTag-attached peptides and PD-L1 antibody, respectively. The modified OMV was able to efficiently conjugate with ESC-derived TAAs and PD-L1 antibody (SpC-OMVs + SpT-peptides + anti-PD-L1), increasing the residence time of TAAs in the body. The results showed that the combination therapy of ESC-based TAAs and PD-L1 antibody delivered by OMV had significant inhibitory effects in mouse tumor model. Specifically, it was effective in reducing tumor growth by enhancing IFN-γ-CD8+ T cell responses and increasing the number of CD8+ memory cells and antigen-specific T cells. Overall, the new OMV delivery system is a versatile platform that can enhance the immune responses of ESC-based TAA cancer vaccines. Graphical Abstract |
| first_indexed | 2024-03-08T16:14:37Z |
| format | Article |
| id | doaj.art-af8fa559a3624a3fbf26a475476946a7 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-08T16:14:37Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-af8fa559a3624a3fbf26a475476946a72024-01-07T12:43:05ZengBMCJournal of Nanobiotechnology1477-31552024-01-0122112010.1186/s12951-023-02273-8Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery systemMeiling Jin0Da Huo1Jingjing Sun2Jingchu HuShuzhen Liu3Mingshuo Zhan4Bao-zhong Zhang5Jian-Dong Huang6Chinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Chinese Academy of SciencesChinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Chinese Academy of SciencesChinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Chinese Academy of SciencesChinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Chinese Academy of SciencesChinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Chinese Academy of SciencesChinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Chinese Academy of SciencesChinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Chinese Academy of SciencesAbstract Embryonic stem cell (ESC)-derived epitopes can act as therapeutic tumor vaccines against different types of tumors Jin (Adv Healthc Mater 2023). However, these epitopes have poor immunogenicity and stimulate insufficient CD8+ T cell responses, which motivated us to develop a new method to deliver and enhance their effectiveness. Bacterial outer membrane vesicles (OMVs) can serve as immunoadjuvants and act as a delivery vector for tumor antigens. In the current study, we engineered a new OMV platform for the co-delivery of ESC-derived tumor antigens and immune checkpoint inhibitors (PD-L1 antibody). An engineered Staphylococcal Protein A (SpA) was created to non-specifically bind to anti-PD-L1 antibody. SpyCatcher (SpC) and SpA were fused into the cell outer membrane protein OmpA to capture SpyTag-attached peptides and PD-L1 antibody, respectively. The modified OMV was able to efficiently conjugate with ESC-derived TAAs and PD-L1 antibody (SpC-OMVs + SpT-peptides + anti-PD-L1), increasing the residence time of TAAs in the body. The results showed that the combination therapy of ESC-based TAAs and PD-L1 antibody delivered by OMV had significant inhibitory effects in mouse tumor model. Specifically, it was effective in reducing tumor growth by enhancing IFN-γ-CD8+ T cell responses and increasing the number of CD8+ memory cells and antigen-specific T cells. Overall, the new OMV delivery system is a versatile platform that can enhance the immune responses of ESC-based TAA cancer vaccines. Graphical Abstracthttps://doi.org/10.1186/s12951-023-02273-8Embryonic stem cellEpitopesTumor immunityOMVsVaccines |
| spellingShingle | Meiling Jin Da Huo Jingjing Sun Jingchu Hu Shuzhen Liu Mingshuo Zhan Bao-zhong Zhang Jian-Dong Huang Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system Journal of Nanobiotechnology Embryonic stem cell Epitopes Tumor immunity OMVs Vaccines |
| title | Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system |
| title_full | Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system |
| title_fullStr | Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system |
| title_full_unstemmed | Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system |
| title_short | Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system |
| title_sort | enhancing immune responses of esc based taa cancer vaccines with a novel omv delivery system |
| topic | Embryonic stem cell Epitopes Tumor immunity OMVs Vaccines |
| url | https://doi.org/10.1186/s12951-023-02273-8 |
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