title: Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus.
abstract: 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.
authors: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors: Patrizia
authors: P
authors: Nanni
authors: Valentina
authors: V
authors: Gatta
authors: Laura
authors: L
authors: Menotti
authors: Carla
authors: C
authors: De Giovanni
authors: Marianna
authors: M
authors: Ianzano
authors: Arianna
authors: A
authors: Palladini
authors: Valentina
authors: V
authors: Grosso
authors: Massimiliano
authors: M
authors: Dall'ora
authors: Stefania
authors: S
authors: Croci
authors: Giordano
authors: G
authors: Nicoletti
authors: Lorena
authors: L
authors: Landuzzi
authors: Manuela
authors: M
authors: Iezzi
authors: Gabriella
authors: G
authors: Campadelli-Fiume
authors: Pier-Luigi
authors: PL
authors: Lollini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
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