Amalgamating oncolytic viruses to enhance their safety, consolidate their killing mechanisms, and accelerate their spread

Camilo Ayala-Breton, Lukkana Suksanpaisan, Emily K. Mader, Stephen J. Russell, Kah Whye Peng

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Oncolytic viruses are structurally and biologically diverse, spreading through tumors and killing them by various mechanisms and with different kinetics. Here, we created a hybrid vesicular stomatitis/measles virus (VSV/MV) that harnesses the safety of oncolytic MV, the speed of VSV, and the tumor killing mechanisms of both viruses. Oncolytic MV targets CD46 and kills by forcing infected cells to fuse with uninfected neighbors, but propagates slowly. VSV spreads rapidly, directly lysing tumor cells, but is neurotoxic and loses oncolytic potency when neuroattenuated by conventional approaches. The hybrid VSV/MV lacks neurotoxicity, replicates rapidly with VSV kinetics, and selectively targets CD46 on tumor cells. Its in vivo performance in a myeloma xenograft model was substantially superior to either MV or widely used recombinant oncolytic VSV-M51.

Original languageEnglish (US)
Pages (from-to)1930-1937
Number of pages8
JournalMolecular Therapy
Volume21
Issue number10
DOIs
StatePublished - Oct 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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