Mechanism of action of over-expressing NY-ESO-1 in vesicular stomatitis virus and its combination therapy with NY-ESO-1 TCR-T
IntroductionVesicular stomatitis virus (VSV) is a promising oncolytic viral platform due to its short replication cycle, broad tissue tropism, low natural infection rate in humans, and a small genome that is easy to genetically manipulate. Leveraging these advantages, we developed an attenuated onco...
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Frontiers Media S.A.
2025-08-01
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| author | Ting Tian Liang Ma Liying Mao Xiangxiang Wang Longxin Cheng Qibin Ma Rong Xu Guoqing Zhou |
| author_facet | Ting Tian Liang Ma Liying Mao Xiangxiang Wang Longxin Cheng Qibin Ma Rong Xu Guoqing Zhou |
| author_sort | Ting Tian |
| collection | DOAJ |
| description | IntroductionVesicular stomatitis virus (VSV) is a promising oncolytic viral platform due to its short replication cycle, broad tissue tropism, low natural infection rate in humans, and a small genome that is easy to genetically manipulate. Leveraging these advantages, we developed an attenuated oncolytic VSV-based virus, OVV-01, encoding the tumor-associated antigen (TAA) NY-ESO-1.MethodsOVV-01 was constructed by inserting the NY-ESO-1 gene into a VSV backbone. In vitro cytotoxicity assays were performed across various tumor cell lines to evaluate its oncolytic activity. The expression and presentation of NY-ESO-1 on infected cells were assessed. In vivo studies using xenograft mouse models were conducted to examine tumor selectivity, T cell activation, and therapeutic efficacy, both alone and in combination with NY-ESO-1-specific TCR-engineered T cells.ResultsOVV-01 efficiently infected and inhibited the growth of multiple tumor cell lines in vitro. The overexpressed NY-ESO-1 was presented on the tumor cell surface and recognized by NY-ESO-1-specific TCR-T cells, promoting targeted cytotoxicity. In vivo, OVV-01 selectively replicated in tumor tissues and induced stronger activation of hCD4⁺, hCD8⁺, and NY-ESO-1-specific TCR-T cells compared to the control virus OVV-00. Combination therapy with OVV-01 and TCR-T cells significantly enhanced tumor control compared to monotherapies.DiscussionOur findings demonstrate that OVV-01 not only possesses potent direct oncolytic activity but also enhances the efficacy of adoptive T cell therapy by improving antigen presentation and T cell activation. This dual mechanism provides a rationale for using OVV-01 in combination immunotherapy strategies targeting solid tumors. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-6d9c0949faa04c0ca386b968124b98ec2025-08-20T03:41:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16179411617941Mechanism of action of over-expressing NY-ESO-1 in vesicular stomatitis virus and its combination therapy with NY-ESO-1 TCR-TTing Tian0Liang Ma1Liying Mao2Xiangxiang Wang3Longxin Cheng4Qibin Ma5Rong Xu6Guoqing Zhou7Research and Development Department, Joint Biosciences (SH) Ltd, Shanghai, ChinaResearch and Development Department, Joint Biosciences (SH) Ltd, Shanghai, ChinaResearch and Development Department, Joint Biosciences (SH) Ltd, Shanghai, ChinaResearch and Development Department, Joint Biosciences (SH) Ltd, Shanghai, ChinaResearch and Development Department, Joint Biosciences (SH) Ltd, Shanghai, ChinaResearch and Development Department, Joint Biosciences (SH) Ltd, Shanghai, ChinaScientific Advisory Board, Joint Biosciences (SH) Ltd, Shanghai, ChinaResearch and Development Department, Joint Biosciences (SH) Ltd, Shanghai, ChinaIntroductionVesicular stomatitis virus (VSV) is a promising oncolytic viral platform due to its short replication cycle, broad tissue tropism, low natural infection rate in humans, and a small genome that is easy to genetically manipulate. Leveraging these advantages, we developed an attenuated oncolytic VSV-based virus, OVV-01, encoding the tumor-associated antigen (TAA) NY-ESO-1.MethodsOVV-01 was constructed by inserting the NY-ESO-1 gene into a VSV backbone. In vitro cytotoxicity assays were performed across various tumor cell lines to evaluate its oncolytic activity. The expression and presentation of NY-ESO-1 on infected cells were assessed. In vivo studies using xenograft mouse models were conducted to examine tumor selectivity, T cell activation, and therapeutic efficacy, both alone and in combination with NY-ESO-1-specific TCR-engineered T cells.ResultsOVV-01 efficiently infected and inhibited the growth of multiple tumor cell lines in vitro. The overexpressed NY-ESO-1 was presented on the tumor cell surface and recognized by NY-ESO-1-specific TCR-T cells, promoting targeted cytotoxicity. In vivo, OVV-01 selectively replicated in tumor tissues and induced stronger activation of hCD4⁺, hCD8⁺, and NY-ESO-1-specific TCR-T cells compared to the control virus OVV-00. Combination therapy with OVV-01 and TCR-T cells significantly enhanced tumor control compared to monotherapies.DiscussionOur findings demonstrate that OVV-01 not only possesses potent direct oncolytic activity but also enhances the efficacy of adoptive T cell therapy by improving antigen presentation and T cell activation. This dual mechanism provides a rationale for using OVV-01 in combination immunotherapy strategies targeting solid tumors.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1617941/fullvesicular stomatitis virusNY-ESO-1tumorTCR-T cellcombination (combined) therapy |
| spellingShingle | Ting Tian Liang Ma Liying Mao Xiangxiang Wang Longxin Cheng Qibin Ma Rong Xu Guoqing Zhou Mechanism of action of over-expressing NY-ESO-1 in vesicular stomatitis virus and its combination therapy with NY-ESO-1 TCR-T Frontiers in Immunology vesicular stomatitis virus NY-ESO-1 tumor TCR-T cell combination (combined) therapy |
| title | Mechanism of action of over-expressing NY-ESO-1 in vesicular stomatitis virus and its combination therapy with NY-ESO-1 TCR-T |
| title_full | Mechanism of action of over-expressing NY-ESO-1 in vesicular stomatitis virus and its combination therapy with NY-ESO-1 TCR-T |
| title_fullStr | Mechanism of action of over-expressing NY-ESO-1 in vesicular stomatitis virus and its combination therapy with NY-ESO-1 TCR-T |
| title_full_unstemmed | Mechanism of action of over-expressing NY-ESO-1 in vesicular stomatitis virus and its combination therapy with NY-ESO-1 TCR-T |
| title_short | Mechanism of action of over-expressing NY-ESO-1 in vesicular stomatitis virus and its combination therapy with NY-ESO-1 TCR-T |
| title_sort | mechanism of action of over expressing ny eso 1 in vesicular stomatitis virus and its combination therapy with ny eso 1 tcr t |
| topic | vesicular stomatitis virus NY-ESO-1 tumor TCR-T cell combination (combined) therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1617941/full |
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