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[Cancer Research 60, 1492-1497, March 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Fusogenic Membrane Glycoproteins As a Novel Class of Genes for the Local and Immune-mediated Control of Tumor Growth1

Andrew Bateman, Francis Bullough, Stephen Murphy, Lisa Emiliusen, Dimitri Lavillette, François-Loic Cosset, Roberto Cattaneo, Stephen J. Russell and Richard G. Vile2

Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905 [A. B., S. M., L. E., R. C., S. J. R., R. G. V.]; Cambridge Genetics Limited, CB4 OF9 Cambridge, United Kingdom [F. B.]; and Vectorologie Retrovirale et Therapie Genique, INSERM U412–Unite de Virologie Humaine Ecole Normale Superieure de Lyon, 69364 Lyon Cedex 07, France [D. L., F-L. C.]

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.




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