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Abstract
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Background: Preclinical and clinical studies show that local and systemic antitumor efficacy is achievable
by in situ vaccination (ISV) using plant virus nanoparticles in which immunostimulatory reagents are directly
administered into the tumor rather than systemically. Aim: To investigate a minimally studied plant
virus nanoparticle, alfalfa mosaic virus (AMV), for ISV treatment of 4T1, the very aggressive andmetastatic
murine triple-negative breast cancer model. Materials & methods: AMV nanoparticles were propagated
and characterized. Their treatment impact on in vivo tumors were analyzed using determination of inherent
immunogenicity, cytokine analysis, western blotting analysis and immunohistochemistry methodologies.
Results: AMV used as an ISV significantly slowed down tumor progression and prolonged survival
through immune mechanisms (p < 0.001). Conclusion: Mechanistic studies show that ISV with AMV increases
costimulatory molecules, inflammatory cytokines and immune effector cell infiltration and downregulates
immune-suppressive molecules.
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