Heterologous prime-boost with an mRNA vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppression
Summary: Therapeutic mRNA vaccines are limited in inducing tumor shrinkage in advanced cancers due to their inability to overcome immune-suppressive mechanisms within tumors. In this study, we developed an HPV-immunogen-expressing oncolytic virus (OV) using HSV-1 for HPV-related cancer treatment. A...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725005169 |
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| author | Kuan Zhang Dong Zuo Zhenglong Wang Jun Ding Jiang Xu Yin Liu Yu Zhong William Jia |
| author_facet | Kuan Zhang Dong Zuo Zhenglong Wang Jun Ding Jiang Xu Yin Liu Yu Zhong William Jia |
| author_sort | Kuan Zhang |
| collection | DOAJ |
| description | Summary: Therapeutic mRNA vaccines are limited in inducing tumor shrinkage in advanced cancers due to their inability to overcome immune-suppressive mechanisms within tumors. In this study, we developed an HPV-immunogen-expressing oncolytic virus (OV) using HSV-1 for HPV-related cancer treatment. A mouse syngeneic tumor model evaluates the effectiveness of intratumoral OV application for E6+E7+ tumors. Comparative analysis of OV and mRNA vaccines reveals distinct mechanisms in tumor treatment. Single-cell RNA sequencing and flow cytometry show that OV enhances cytotoxic T cell infiltration, polarizes neutrophils and macrophages toward anti-tumor phenotypes, and promotes immune activation within the tumor. In contrast, the mRNA vaccine more effectively activates peripheral antigen-specific T cell responses. A heterologous prime-boost strategy using the mRNA vaccine to prime systemic T cells, followed by OV therapy to direct these cells into the tumor, leads to significant tumor regression. This combination optimizes both systemic and intratumoral immune responses for advanced HPV-related cancers. |
| format | Article |
| id | doaj-art-5d3b459e80b94ff7bc7a356226e0aae8 |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-5d3b459e80b94ff7bc7a356226e0aae82025-08-20T03:08:55ZengElsevierCell Reports2211-12472025-06-0144611574510.1016/j.celrep.2025.115745Heterologous prime-boost with an mRNA vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppressionKuan Zhang0Dong Zuo1Zhenglong Wang2Jun Ding3Jiang Xu4Yin Liu5Yu Zhong6William Jia7Shanghai Virogin Biotech Co., Ltd., Shanghai 201802, ChinaShanghai Virogin Biotech Co., Ltd., Shanghai 201802, ChinaShanghai Virogin Biotech Co., Ltd., Shanghai 201802, ChinaShanghai Virogin Biotech Co., Ltd., Shanghai 201802, China; Virogin Biotech Co., Ltd, Richmond, BC V6V 3A4, CanadaShanghai Virogin Biotech Co., Ltd., Shanghai 201802, ChinaShanghai Virogin Biotech Co., Ltd., Shanghai 201802, ChinaShanghai Virogin Biotech Co., Ltd., Shanghai 201802, ChinaShanghai Virogin Biotech Co., Ltd., Shanghai 201802, China; Virogin Biotech Co., Ltd, Richmond, BC V6V 3A4, Canada; Corresponding authorSummary: Therapeutic mRNA vaccines are limited in inducing tumor shrinkage in advanced cancers due to their inability to overcome immune-suppressive mechanisms within tumors. In this study, we developed an HPV-immunogen-expressing oncolytic virus (OV) using HSV-1 for HPV-related cancer treatment. A mouse syngeneic tumor model evaluates the effectiveness of intratumoral OV application for E6+E7+ tumors. Comparative analysis of OV and mRNA vaccines reveals distinct mechanisms in tumor treatment. Single-cell RNA sequencing and flow cytometry show that OV enhances cytotoxic T cell infiltration, polarizes neutrophils and macrophages toward anti-tumor phenotypes, and promotes immune activation within the tumor. In contrast, the mRNA vaccine more effectively activates peripheral antigen-specific T cell responses. A heterologous prime-boost strategy using the mRNA vaccine to prime systemic T cells, followed by OV therapy to direct these cells into the tumor, leads to significant tumor regression. This combination optimizes both systemic and intratumoral immune responses for advanced HPV-related cancers.http://www.sciencedirect.com/science/article/pii/S2211124725005169CP: ImmunologyCP: Cancer |
| spellingShingle | Kuan Zhang Dong Zuo Zhenglong Wang Jun Ding Jiang Xu Yin Liu Yu Zhong William Jia Heterologous prime-boost with an mRNA vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppression Cell Reports CP: Immunology CP: Cancer |
| title | Heterologous prime-boost with an mRNA vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppression |
| title_full | Heterologous prime-boost with an mRNA vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppression |
| title_fullStr | Heterologous prime-boost with an mRNA vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppression |
| title_full_unstemmed | Heterologous prime-boost with an mRNA vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppression |
| title_short | Heterologous prime-boost with an mRNA vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppression |
| title_sort | heterologous prime boost with an mrna vaccine and an oncolytic virus enhances tumor regression through overcoming intratumoral immune suppression |
| topic | CP: Immunology CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725005169 |
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