Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth

Andrew Bateman, Francis Bullough, Stephen Murphy, Lisa Emiliusen, Dimitri Lavillette, François Loic Cosset, Roberto Cattaneo, Stephen J. Russell, Richard G. Vile

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

We report here the use of viral fusogenic membrane glycoproteins (FMGs) as a new class of therapeutic genes for the control of tumor growth. FMGs kill cells by fusing them into large multinucleated syncytia, which die by sequestration of cell nuclei and subsequent nuclear fusion by a mechanism that is nonapoptotic, as assessed by multiple criteria. Direct and bystander killing of three different FMGs were at least one log more potent than that of herpes simplex virus thymidine kinase or cytosine deaminase suicide genes. Transduction of human tumor xenografts with plasmid DNA prevented tumor outgrowth in vivo, and cytotoxicity could be regulated through transcriptional targeting. Syncytial formation is accompanied by the induction of immunostimulatory heat shock proteins, and tumor-associated FMG expression in immunocompetent animals generated specific antitumor immunity.

Original languageEnglish (US)
Pages (from-to)1492-1497
Number of pages6
JournalCancer research
Volume60
Issue number6
StatePublished - Mar 15 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth'. Together they form a unique fingerprint.

  • Cite this