title: Capacity of wild-type and chemokine-armed parvovirus H-1PV for inhibiting neo-angiogenesis.
abstract: Anti-angiogenic therapy has been recognized as a powerful potential strategy for impeding the growth of various tumors. However no major therapeutic effects have been observed to date, mainly because of the emergence of several resistance mechanisms. Among novel strategies to target tumor vasculature, some oncolytic viruses open up new prospects. In this context, we addressed the question whether the rodent parvovirus H-1PV can target endothelial cells. We show that cultures of human normal (HUVEC) and immortalized (KS-IMM) endothelial cells sustain an abortive viral cycle upon infection with H-1PV and are sensitive to H-1PV cytotoxicity. H-1PV significantly inhibits infected KS-IMM tumor growth. This effect may be traced back by the virus ability to both kill proliferating endothelial cells and inhibit VEGF production Recombinant H-1PV vectors can also transduce tumor cells with chemokines endowed with anti-angiogenesis properties, and warrant further validation for the treatment of highly vascularized tumors.
authors.affiliation: Tumor Virology Division, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Muriel
authors.initials: M
authors.lastname: Lavie
authors.forename: Sofie
authors.initials: S
authors.lastname: Struyf
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stroh-Dege
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
authors.forename: Christiane
authors.initials: C
authors.lastname: Dinsart
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D017992:Parvovirus / Q000502:physiology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018925:Chemokines
keywords: Angiogenesis; Cancer therapy; Chemokine; Kaposi sarcoma; Parvovirus