title: Myeloid-derived suppressor cells as a vehicle for tumor-specific oncolytic viral therapy.
abstract: One of the several impediments to effective oncolytic virus therapy of cancer remains a lack of tumor-specific targeting. Myeloid-derived suppressor cells (MDSC) are immature myeloid cells induced by tumor factors in tumor-bearing hosts. The biodistribution kinetics of MDSC and other immune cell types in a murine hepatic colon cancer model was investigated through the use of tracking markers and MRI. MDSCs were superior to other immune cell types in preferential migration to tumors in comparison with other tissues. On the basis of this observation, we engineered a strain of vesicular stomatitis virus (VSV), an oncolytic rhabdovirus that bound MDSCs and used them as a delivery vehicle. Improving VSV-binding efficiency to MDSCs extended the long-term survival of mice bearing metastatic colon tumors compared with systemic administration of wild-type VSV alone. Survival was further extended by multiple injections of the engineered virus without significant toxicity. Notably, direct tumor killing was accentuated by promoting MDSC differentiation towards the classically activated M1-like phenotype. Our results offer a preclinical proof-of-concept for using MDSCs to facilitate and enhance the tumor-killing activity of tumor-targeted oncolytic therapeutics.
authors.affiliation: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Eisenstein
authors.forename: Brian A
authors.initials: BA
authors.lastname: Coakley
authors.forename: Karen
authors.initials: K
authors.lastname: Briley-Saebo
authors.forename: Ge
authors.initials: G
authors.lastname: Ma
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Chen
authors.forename: Marcia
authors.initials: M
authors.lastname: Meseck
authors.forename: Stephen
authors.initials: S
authors.lastname: Ward
authors.forename: Celia
authors.initials: C
authors.lastname: Divino
authors.forename: Savio
authors.initials: S
authors.lastname: Woo
authors.forename: Shu-Hsia
authors.initials: SH
authors.lastname: Chen
authors.forename: Ping-Ying
authors.initials: PY
authors.lastname: Pan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003110:Colonic Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism / Q000821:virology*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D014018:Tissue Distribution; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism*; D056189:Viral Tropism / Q000235:genetics
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