title: Systemic delivery of (gamma1)34.5-deleted herpes simplex virus-1 selectively targets and treats distant human xenograft tumors that express high MEK activity.
abstract: Deltagamma(1)34.5 mutant herpes simplex type 1 viruses are under active clinical investigation as oncolytic therapy for cancer. Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) activity has been shown to suppress protein kinase R and thereby confer oncolytic susceptibility to some human tumors by R3616, a virus deleted for both copies of gamma(1)34.5. We report that systemic delivery of R3616 can selectively target and destroy human xenograft tumors that overexpress MEK activity compared with tumors that express lower MEK activity. These results suggest systemic delivery of R3616 may be effective in the treatment of some human tumors.
authors.affiliation: Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jula
authors.initials: J
authors.lastname: Veerapong
authors.forename: Kai A
authors.initials: KA
authors.lastname: Bickenbach
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Shao
authors.forename: Kerrington D
authors.initials: KD
authors.lastname: Smith
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Posner
authors.forename: Bernard
authors.initials: B
authors.lastname: Roizman
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
mesh_terms: D000818:Animals; D017353:Gene Deletion; D005818:Genetic Engineering; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000032:analysis; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays