Alfalfa mosaic virus nanoparticles-based in situ vaccination induces antitumor immune responses in breast cancer model

基于苜蓿花叶病毒纳米粒子的原位疫苗接种在乳腺癌模型中诱导抗肿瘤免疫反应

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作者:Mehdi Shahgolzari, Maghsoud Pazhouhandeh, Morteza Milani, Steven Fiering, Ahmad Yari Khosroushahi

Aim

To investigate a minimally studied plant virus nanoparticle, alfalfa mosaic virus (AMV), for ISV treatment of 4T1, the very aggressive and metastatic murine triple-negative breast cancer model. Materials &

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.

Conclusion

Mechanistic studies show that ISV with AMV increases costimulatory molecules, inflammatory cytokines and immune effector cell infiltration and downregulates immune-suppressive molecules.

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).

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