Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity

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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Bibliographic Details
Main Authors: Geqiang Zhang, Jun Tu, Yu Zhang, Jianli He, Guoyuan Peng, Qiuju Fan, Yirong Zhang, Mingming Zhang, Hongsheng Tan, Yingjie Xu, Jinke Cheng
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
MT: Delivery Strategies
mRNA
VEGF-B
T cell
immunotherapy
tumor microenvironment
Online Access:http://www.sciencedirect.com/science/article/pii/S216225312500174X
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Summary: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.
ISSN:2162-2531

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