Treatment of implanted mammary tumors with recombinant vesicular stomatitis virus targeted to Her2/neu.
Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We have created a recombinant replicating VSV (rrVSV) that targeted to Her2/neu expressing breast cancer cells and expresses mouse GM-CSF. We now tested the efficacy of this rrVSV in the treatment of peritoneal tumor implants of D2F2/E2 cells, a BALB/c mouse mammary tumor cell line, which was stably transfected to express Her2/neu. Mice were treated 1 day following tumor implantation with either 2 x 10(8) infectious doses rrVSV or conditioned media (CM). All control animals developed massive peritoneal tumor with a median survival of 16 days. Nine of 10 rrVSV treated mice survived long term with no evidence of tumor. rrVSV had much less efficacy in treating implants of the parent D2F2 cells that did not express Her2/neu. The median survival was 13.5 days in mice treated with CM and 21 days in those treated with rrVSV. There was one long term survivor in the rrVSV treated group. None of the rrVSV treated animals showed evidence of viral toxicity. Three of 7 long term survivors did not develop tumor when rechallenged first with D2F2/E2 and then with D2F2 cells. Both successful therapy and resistance to rechallenge were T-cell dependent. These studies demonstrate that targeted rrVSV eliminated peritoneal implants of Her2/neu expressing tumor and elicited an anti-tumor T-cell immunologic response.
Bergman
Ira
I
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ira.bergman@chp.edu
Griffin
Judith A
JA
Gao
Yanhua
Y
Whitaker-Dowling
Patricia
P
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000502:physiology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins