Gene therapy of ovarian cancer with IFN-alpha-producing fibroblasts: comparison of constitutive and inducible vectors

Gene Therapy
Stefano IndraccoloAlberto Amadori

Abstract

Ovarian cancer represents a malignancy suitable for cell and gene therapy approaches owing to its containment within the peritoneal cavity, even at advanced tumor stages. As regulation of transgene expression would be preferable for conducting clinical trials for reasons of safety, we investigated whether intraperitoneal (i.p.) administration of retroviral vector-transduced fibroblasts encoding murine interferon-alpha (IFN-alpha) could have therapeutic activity, and compared its effect with the antitumor effects of fibroblasts producing IFN-alpha under a rapamycin analogue (AP21967)-inducible promoter. Human and murine fibroblasts were recruited into the solid component of transplantable ovarian cancer-grown i.p. in severe combined immunodeficiency mice. Multiple administrations of fibroblasts producing IFN-alpha in a constitutive manner showed therapeutic efficacy, leading to significant prolongation of survival in the majority of animals, associated with inhibition of tumor angiogenesis. Compared to cells transduced by the constitutive vector, fibroblasts transduced by the inducible vector released twofold higher IFN-alpha levels in vitro, following induction by AP21967, and production of the cytokine was under pharmacologic ...Continue Reading

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Citations

Apr 13, 2010·Clinical & Experimental Metastasis·Adriana AlbiniUlrich Pfeffer
Nov 8, 2008·Cancer Gene Therapy·B LortalB Couderc
Jan 28, 2014·Tissue Engineering. Part C, Methods·Christopher G WilsonRenny T Franceschi
Apr 29, 2009·Journal of Experimental & Clinical Cancer Research : CR·Bo ZhangYan Wang
Nov 21, 2009·Journal of the American Academy of Dermatology·Amy NguyenKristen M Kelly
Feb 20, 2007·Molecular Aspects of Medicine·Luca PersanoStefano Indraccolo
Feb 20, 2007·Molecular Aspects of Medicine·Sonia MinuzzoAlberto Amadori
Jul 25, 2014·Chemical Communications : Chem Comm·Maximilian HörnerWilfried Weber

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