Alfalfa mosaic virus nanoparticles-based in situ vaccination induces antitumor immune responses in breast cancer model.
Alfalfa mosaic virus nanoparticles-based in situ vaccination induces antitumor immune responses in breast cancer model.
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DOI：
10.2217/nnm-2020-0311
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发表时间：
2021-01
期刊：
影响因子：
5.5
通讯作者：
M. Shahgolzari;M. Pazhouhandeh;M. Milani;S. Fiering;A. Khosroushahi
中科院分区：
文献类型：
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作者：
M. Shahgolzari;M. Pazhouhandeh;M. Milani;S. Fiering;A. Khosroushahi
背景：临床前和临床研究表明，通过使用植物病毒纳米颗粒进行原位疫苗接种（ISV）可以实现局部和全身抗肿瘤功效，其中免疫刺激试剂直接施用到肿瘤中而不是全身。目的：研究一种经过最少研究的植物病毒纳米颗粒——苜蓿花叶病毒 (AMV)，用于 ISV 治疗 4T1（一种极具侵袭性和转移性的小鼠三阴性乳腺癌模型）。材料和方法：AMV 纳米粒子的繁殖和表征。使用固有免疫原性测定、细胞因子分析、蛋白质印迹分析和免疫组织化学方法来分析它们对体内肿瘤的治疗影响。结果：AMV 用作 ISV，通过免疫机制显着减缓肿瘤进展并延长生存期 (p < 0.001)。结论：机制研究表明，含有 AMV 的 ISV 会增加共刺激分子、炎症细胞因子和免疫效应细胞浸润，并下调免疫抑制分子。
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 and metastatic 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.