title: Amalgamating oncolytic viruses to enhance their safety, consolidate their killing mechanisms, and accelerate their spread.
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.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Ayala-Breton
authors.forename: Lukkana
authors.initials: L
authors.lastname: Suksanpaisan
authors.forename: Emily K
authors.initials: EK
authors.lastname: Mader
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Kah-Whye
authors.initials: KW
authors.lastname: Peng
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D016466:CHO Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003412:Cricetulus; D004195:Disease Models, Animal; D005818:Genetic Engineering; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D051916:Membrane Cofactor Protein / Q000187:drug effects*; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000473:pathology / Q000628:therapy*; D009474:Neurons / Q000473:pathology / Q000821:virology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D051916:Membrane Cofactor Protein