Article: article from journal or magazin.
Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer.
Clinical Cancer Research
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Epithelial ovarian cancer (EOC) remains localized within the peritoneal cavity in a large number of patients, lending itself to i.p. approaches of therapy. In the present study, we investigated the effect of replication-selective herpes simplex virus-1 (HSV-1) used as an oncolytic agent against EOC and the use of human teratocarcinoma PA-1 as carrier cells for i.p. therapy. HSV-1716, a replication-competent attenuated strain lacking ICP34.5, caused a direct dose-dependent oncolytic effect on EOC cells in vitro. A single i.p. administration of 5 x 10(6) plaque-forming units resulted in a significant reduction of tumor volume and tumor spread and an increase in survival in a mouse xenograft model. PA-1 cells supported HSV replication in vitro and bound preferentially to human ovarian carcinoma surfaces compared with mesothelial surfaces in vitro and in vivo. In comparison with the administration of HSV-1716 alone, irradiated PA-1 cells, infected at two multiplicities of infection with HSV-1716 and injected i.p. at 5 x 10(6) cells/animal, led to a significant tumor reduction in the two models tested and the significant prolongation of mean survival in one model. Histological evaluation revealed extensive necrosis in tumor areas infected by HSV-1716. Immunohistochemistry against HSV-1 revealed areas of viral infection within tumor nodules, which persisted for several weeks after treatment. Administration of HSV-infected PA-1 carrier cells resulted in larger areas of tumor infected by the virus. Our results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on EOC, which may be further enhanced by the utilization of a delivery system with carrier cells, based on amplification of the viral load and possibly on preferential binding of carrier cells to tumor surfaces.
Animals, Cell Adhesion, Cell Survival/radiation effects, Cytopathogenic Effect, Viral, Female, Herpes Simplex/pathology, Herpes Simplex/virology, Humans, Immunohistochemistry, Injections, Intraperitoneal, Mice, Mice, SCID, Neoplasm Transplantation, Neoplasms, Glandular and Epithelial/metabolism, Neoplasms, Glandular and Epithelial/mortality, Neoplasms, Glandular and Epithelial/virology, Ovarian Neoplasms/metabolism, Ovarian Neoplasms/mortality, Ovarian Neoplasms/</QualifierName> <QualifierName MajorTopicYN="N">, Simplexvirus/genetics, Survival Rate, Teratocarcinoma/pathology, Teratocarcinoma/virology, Tumor Cells, Cultured, Virus Replication
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