Shahgolzari Mehdi, Pazhouhandeh Maghsoud, Milani Morteza, Fiering Steven, Khosroushahi Ahmad Yari
Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Nanomedicine (Lond). 2021 Jan;16(2):97-107. doi: 10.2217/nnm-2020-0311. Epub 2021 Jan 14.
Preclinical and clinical studies show that local and systemic antitumor efficacy is achievable by vaccination (ISV) using plant virus nanoparticles in which immunostimulatory reagents are directly administered into the tumor rather than systemically. 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. AMV nanoparticles were propagated and characterized. Their treatment impact on tumors were analyzed using determination of inherent immunogenicity, cytokine analysis, western blotting analysis and immunohistochemistry methodologies. AMV used as an ISV significantly slowed down tumor progression and prolonged survival through immune mechanisms (p < 0.001). Mechanistic studies show that ISV with AMV increases costimulatory molecules, inflammatory cytokines and immune effector cell infiltration and downregulates immune-suppressive molecules.
临床前和临床研究表明，通过使用植物病毒纳米颗粒进行瘤内接种疫苗（ISV），而非全身给药，可实现局部和全身抗肿瘤疗效。为了研究一种研究较少的植物病毒纳米颗粒——苜蓿花叶病毒（AMV），用于ISV治疗极具侵袭性和转移性的小鼠三阴性乳腺癌模型4T1。对AMV纳米颗粒进行了繁殖和表征。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分析了它们对肿瘤的治疗影响。用作ISV的AMV通过免疫机制显著减缓了肿瘤进展并延长了生存期（p<0.001）。机制研究表明，AMV介导的ISV增加了共刺激分子、炎性细胞因子和免疫效应细胞浸润，并下调了免疫抑制分子。
