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 Geoffrey Vile

Research output: Contribution to journalArticle

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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

Fingerprint

Membrane Glycoproteins
Growth
Genes
Neoplasms
Nuclear Fusion
Cytosine Deaminase
Thymidine Kinase
Simplexvirus
Giant Cells
Heat-Shock Proteins
Cell Nucleus
Heterografts
Suicide
Immunity
Plasmids
DNA
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bateman, A., Bullough, F., Murphy, S., Emiliusen, L., Lavillette, D., Cosset, F. L., ... Vile, R. G. (2000). Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. Cancer Research, 60(6), 1492-1497.

Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. / Bateman, Andrew; Bullough, Francis; Murphy, Stephen; Emiliusen, Lisa; Lavillette, Dimitri; Cosset, François Loic; Cattaneo, Roberto; Russell, Stephen J; Vile, Richard Geoffrey.

In: Cancer Research, Vol. 60, No. 6, 15.03.2000, p. 1492-1497.

Research output: Contribution to journalArticle

Bateman, A, Bullough, F, Murphy, S, Emiliusen, L, Lavillette, D, Cosset, FL, Cattaneo, R, Russell, SJ & Vile, RG 2000, 'Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth', Cancer Research, vol. 60, no. 6, pp. 1492-1497.
Bateman A, Bullough F, Murphy S, Emiliusen L, Lavillette D, Cosset FL et al. Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. Cancer Research. 2000 Mar 15;60(6):1492-1497.
Bateman, Andrew ; Bullough, Francis ; Murphy, Stephen ; Emiliusen, Lisa ; Lavillette, Dimitri ; Cosset, François Loic ; Cattaneo, Roberto ; Russell, Stephen J ; Vile, Richard Geoffrey. / Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. In: Cancer Research. 2000 ; Vol. 60, No. 6. pp. 1492-1497.
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