Interferon-α gene therapy by lentiviral vectors contrasts ovarian cancer growth through angiogenesis inhibition

Stefano Indraccolo, Veronica Tisato, Valeria Tosello, Walter Habeler, Giovanni Esposito, Lidia Moserle, Laura Stievano, Luca Persano, Luigi Chieco-Bianchi, Alberto Amadori

Research output: Contribution to journalArticle

Abstract

Ovarian cancer represents a suitable disease for gene therapy because of the containment of neoplastic cells in the peritoneal cavity even at advanced tumor stages. The aim of this study was to investigate whether intraperitoneal administration of a lentiviral vector encoding murine interferon-α (LV-IFN) could have therapeutic activity in a transplantable ovarian cancer model. Multiple injections of low amounts of LV-IFN into severe combined immunodeficiency (SCID) mice bearing IGROV-1 or OC316 ovarian cancer cells elicited remarkable antitumor activity, leading to prolongation of survival in the majority of animals. A definitive cure was obtained in animals bearing PD-OVA#1 tumors, generated by injecting tumor cells isolated from the ascitic fluid of a patient into SCID mice. Interferon-α levels were detected in the peritoneal fluids but not in the serum of treated mice, indicating that production of the cytokine is mainly local, by both tumor and normal cells of the host. Antitumor effects were associated with a remarkable decrease in the formation of hemorrhagic ascites, an increase in ischemic tumor necrosis, and a reduction in microvessel density. In conclusion, our findings show that intracavitary IFN-α gene therapy, using a lentiviral vector, provides strong antitumor effects in murine models of ovarian cancer and reinforces the evidence that angiogenesis inhibition is a promising strategy for the treatment of localized tumors.

Original languageEnglish
Pages (from-to)957-970
Number of pages14
JournalHuman Gene Therapy
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 2005

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Interferon-α gene therapy by lentiviral vectors contrasts ovarian cancer growth through angiogenesis inhibition'. Together they form a unique fingerprint.

  • Cite this