Preclinical therapy of disseminated HER-2⁺ 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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2013
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oai:doaj.org-article:45fe9d4027634cfe86e1eaff9514f27a2021-11-18T06:06:05ZPreclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus.1553-73661553-737410.1371/journal.ppat.1003155https://doaj.org/article/45fe9d4027634cfe86e1eaff9514f27a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23382683/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Oncolytic 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⁻/⁻;Il2rg⁻/⁻ 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.Patrizia NanniValentina GattaValentina GattaLaura MenottiCarla De GiovanniMarianna IanzanoArianna PalladiniValentina GrossoMassimiliano Dall'oraStefania CrociGiordano NicolettiLorena LanduzziManuela IezziGabriella Campadelli-FiumePier-Luigi LolliniPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 1, p e1003155 (2013) |
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| collection |
DOAJ |
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EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Patrizia Nanni Valentina Gatta Valentina Gatta Laura Menotti Carla De Giovanni Marianna Ianzano Arianna Palladini Valentina Grosso Massimiliano Dall'ora Stefania Croci Giordano Nicoletti Lorena Landuzzi Manuela Iezzi Gabriella Campadelli-Fiume Pier-Luigi Lollini Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. |
| description |
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⁻/⁻;Il2rg⁻/⁻ 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. |
| format |
article |
| author |
Patrizia Nanni Valentina Gatta Valentina Gatta Laura Menotti Carla De Giovanni Marianna Ianzano Arianna Palladini Valentina Grosso Massimiliano Dall'ora Stefania Croci Giordano Nicoletti Lorena Landuzzi Manuela Iezzi Gabriella Campadelli-Fiume Pier-Luigi Lollini |
| author_facet |
Patrizia Nanni Valentina Gatta Valentina Gatta Laura Menotti Carla De Giovanni Marianna Ianzano Arianna Palladini Valentina Grosso Massimiliano Dall'ora Stefania Croci Giordano Nicoletti Lorena Landuzzi Manuela Iezzi Gabriella Campadelli-Fiume Pier-Luigi Lollini |
| author_sort |
Patrizia Nanni |
| title |
Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. |
| title_short |
Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. |
| title_full |
Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. |
| title_fullStr |
Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. |
| title_full_unstemmed |
Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. |
| title_sort |
preclinical therapy of disseminated her-2⁺ ovarian and breast carcinomas with a her-2-retargeted oncolytic herpesvirus. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/45fe9d4027634cfe86e1eaff9514f27a |
| work_keys_str_mv |
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| _version_ |
1718424533362278400 |