Preclinical therapy of disseminated [HER-2.sup.+] ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus

Oncolytic viruses aim to specifically kill tumor cells. A major challenge is the effective targeting of disseminated tumors in vivo. We retargeted herpes simplex virus (HSV) tropism to HER-2 oncoprotein p185, overexpressed in ovary and breast cancers. The HER-2-retargeted R-LM249 exclusively infects...

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Bibliographic Details
Published in:PLoS Pathogens 2013, Vol.9 (1)
Main Authors: Nanni, Patrizia, Gatta, Valentina, Menotti, Laura, De Giovanni, Carla, Ianzano, Marianna, Palladini, Arianna, Grosso, Valentina, DallOra, Massimiliano, Croci, Stefania, Nicoletti, Giordano, Landuzzi, Lorena, Iezzi, Manuela, Campadelli-Fiume, Gabriella, Lollini, Pier-Luigi
Format: Report
Language:English
Subjects:
Breast cancer
Cancer
Carcinoma
Care and treatment
Health aspects
Herpesviruses
Ovarian cancer
Physiological aspects
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Summary:Oncolytic viruses aim to specifically kill tumor cells. A major challenge is the effective targeting of disseminated tumors in vivo. We retargeted herpes simplex virus (HSV) tropism to HER-2 oncoprotein p185, overexpressed in ovary and breast cancers. The HER-2-retargeted R-LM249 exclusively infects and kills tumor cells expressing high levels of human HER-2. Here, we assessed the efficacy of systemically i.p. delivered R-LM249 against disseminated tumors in mouse models that recapitulate tumor spread to the peritoneum in women. The human ovarian carcinoma SK-OV-3 cells implanted intraperitoneally (i.p.) in immunodeficient [Rag2.sup.-/-];[Il2rg.sup.-/-] mice gave rise to a progressive peritoneal carcinomatosis which mimics the fatal condition in advanced human patients. I.p. administration of R-LM249 strongly inhibited carcinomatosis, resulting in 60% of mice free from peritoneal diffusion, and 95% reduction in the total weight of neoplastic nodules. Intraperitoneal metastases are a common outcome in breast cancer: i.p. administration of R-LM249 strongly inhibited the growth of ovarian metastases of HER-2+ MDA-MB-453 breast cells. Brain metastases were also reduced. Cumulatively, upon i.p. administration the HER-2-redirected oncolytic HSV effectively reduced the growth of ovarian and breast carcinoma disseminated to the peritoneal cavity.
ISSN:1553-7366
DOI:10.1371/journal.ppat.1003155