Myeloid-derived suppressor cells as a vehicle for tumor-specific oncolytic viral therapy

Samuel Eisenstein, Brian A. Coakley, Karen Briley-Saebo, Ge Ma, Hui Ming Chen, Marcia Meseck, Stephen Ward, Celia Divino, Savio Woo, Shu Hsia Chen, Ping Ying Pan

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

One of the several impediments to effective oncolytic virus therapy of cancer remains a lack of tumorspecific 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-ofconcept for using MDSCs to facilitate and enhance the tumor-killing activity of tumor-targeted oncolytic therapeutics.

Original languageEnglish (US)
Pages (from-to)5003-5015
Number of pages13
JournalCancer research
Volume73
Issue number16
DOIs
StatePublished - Aug 15 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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