Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity
The advancement of mRNA-based cancer immunotherapies has gained significant momentum, particularly after the success of mRNA vaccines during the COVID-19 pandemic and the recognition of mRNA vaccine development with the 2023 Nobel Prize. mRNA encoding cytokines, antibodies, and chimeric antigen rece...
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S216225312500174X |
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| author | Geqiang Zhang Jun Tu Yu Zhang Jianli He Guoyuan Peng Qiuju Fan Yirong Zhang Mingming Zhang Hongsheng Tan Yingjie Xu Jinke Cheng |
| author_facet | Geqiang Zhang Jun Tu Yu Zhang Jianli He Guoyuan Peng Qiuju Fan Yirong Zhang Mingming Zhang Hongsheng Tan Yingjie Xu Jinke Cheng |
| author_sort | Geqiang Zhang |
| collection | DOAJ |
| description | The advancement of mRNA-based cancer immunotherapies has gained significant momentum, particularly after the success of mRNA vaccines during the COVID-19 pandemic and the recognition of mRNA vaccine development with the 2023 Nobel Prize. mRNA encoding cytokines, antibodies, and chimeric antigen receptor T cells has demonstrated substantial therapeutic potential in both preclinical models and clinical trials. Previous study identified vascular endothelial growth factor B (VEGF-B) as a metabolic regulator that controls lipid synthesis and maintains mitochondrial membrane integrity, essential for the survival of activated T cells. In this study, we demonstrate that mRNA encoding VEGF-B, delivered to tumors via lipid nanoparticles, effectively controls tumor growth in both subcutaneous and lung metastasis tumor models. Combination with programmed death-1 blockade significantly amplified therapeutic efficacy, leading to complete tumor regression in the lung metastasis model. Immune profiling revealed that nanoparticle delivery of VEGF-B mRNA reprograms the tumor microenvironment by increasing CD8+ T cell infiltration and enhancing the expression of effector molecules, including interferon-γ, tumor necrosis factor alpha, and granzyme B, while downregulating the exhaustion molecule programmed death-1. These findings highlight the considerable promise of mRNA-based therapies in reshaping the tumor microenvironment and enhancing cancer immunotherapy outcomes. |
| format | Article |
| id | doaj-art-40ccab06ec9a4337a2dcdebab55bf5d5 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-40ccab06ec9a4337a2dcdebab55bf5d52025-08-20T03:50:58ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-09-0136310262010.1016/j.omtn.2025.102620Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunityGeqiang Zhang0Jun Tu1Yu Zhang2Jianli He3Guoyuan Peng4Qiuju Fan5Yirong Zhang6Mingming Zhang7Hongsheng Tan8Yingjie Xu9Jinke Cheng10Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Corresponding author: Jun Tu, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China.Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Corresponding author: Hongsheng Tan, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China.Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Corresponding author: Yingjie Xu, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, Hainan 571199, China; Corresponding author: Jinke Cheng, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 200025, China.The advancement of mRNA-based cancer immunotherapies has gained significant momentum, particularly after the success of mRNA vaccines during the COVID-19 pandemic and the recognition of mRNA vaccine development with the 2023 Nobel Prize. mRNA encoding cytokines, antibodies, and chimeric antigen receptor T cells has demonstrated substantial therapeutic potential in both preclinical models and clinical trials. Previous study identified vascular endothelial growth factor B (VEGF-B) as a metabolic regulator that controls lipid synthesis and maintains mitochondrial membrane integrity, essential for the survival of activated T cells. In this study, we demonstrate that mRNA encoding VEGF-B, delivered to tumors via lipid nanoparticles, effectively controls tumor growth in both subcutaneous and lung metastasis tumor models. Combination with programmed death-1 blockade significantly amplified therapeutic efficacy, leading to complete tumor regression in the lung metastasis model. Immune profiling revealed that nanoparticle delivery of VEGF-B mRNA reprograms the tumor microenvironment by increasing CD8+ T cell infiltration and enhancing the expression of effector molecules, including interferon-γ, tumor necrosis factor alpha, and granzyme B, while downregulating the exhaustion molecule programmed death-1. These findings highlight the considerable promise of mRNA-based therapies in reshaping the tumor microenvironment and enhancing cancer immunotherapy outcomes.http://www.sciencedirect.com/science/article/pii/S216225312500174XMT: Delivery StrategiesmRNAVEGF-BT cellimmunotherapytumor microenvironment |
| spellingShingle | Geqiang Zhang Jun Tu Yu Zhang Jianli He Guoyuan Peng Qiuju Fan Yirong Zhang Mingming Zhang Hongsheng Tan Yingjie Xu Jinke Cheng Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity Molecular Therapy: Nucleic Acids MT: Delivery Strategies mRNA VEGF-B T cell immunotherapy tumor microenvironment |
| title | Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity |
| title_full | Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity |
| title_fullStr | Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity |
| title_full_unstemmed | Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity |
| title_short | Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity |
| title_sort | nanoparticle delivery of vegf b mrna promotes t cell infiltration within tumor and triggers robust antitumor immunity |
| topic | MT: Delivery Strategies mRNA VEGF-B T cell immunotherapy tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S216225312500174X |
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