Mehdi Shahgolzari1,2, Maghsoud Pazhouhandeh3, Morteza Milani1, Steven Fiering4,5, Ahmad Yari Khosroushahi1,2. 1. Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Biotechnology Dept. Agriculture Fac. Azarbaijan Shahid Madani University, Tabriz, Iran. 4. Department of Microbiology & Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03756, USA. 5. Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth & Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Abstract
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.
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.