title: Tumor necrosis factor alpha-gene therapy for an established murine melanoma using RGD (Arg-Gly-Asp) fiber-mutant adenovirus vectors.
abstract: Although adenovirus vectors (Ad) provide high-level transduction efficacy to many cell types, extremely high doses of Ad are required for sufficient gene transduction into several tumors, including melanoma. Here, we demonstrated that the expression of coxsackie-adenovirus receptor, a primitive Ad-receptor, was very low in murine and human melanoma cells. We also found that fiber-mutant Ad containing the Arg-Gly-Asp (RGD) sequence in the fiber knob remarkably augmented gene transduction efficacy in melanoma cells by targeting alpha(v)-integrins. In addition, intratumoral injection of RGD fiber-mutant Ad containing the tumor necrosis factor alpha gene (Ad-RGD-TNFalpha) revealed dramatic anti-tumor efficacy through hemolytic necrosis in an established murine B16 BL6 melanoma model. Ad-RGD-TNFalpha required one-tenth the dosage of Ad-TNFalpha to induce an equal therapeutic effect. These results suggest that alpha(v)-integrin-targeted Ad will be a very powerful tool for the advancement of melanoma gene therapy.
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Hyogo 663-8179, Japan.
authors: Yuka
authors: Y
authors: Okada
authors: Naoki
authors: N
authors: Okada
authors: Shinsaku
authors: S
authors: Nakagawa
authors: Hiroyuki
authors: H
authors: Mizuguchi
authors: Koichi
authors: K
authors: Takahashi
authors: Nobuyasu
authors: N
authors: Mizuno
authors: Takuya
authors: T
authors: Fujita
authors: Akira
authors: A
authors: Yamamoto
authors: Takao
authors: T
authors: Hayakawa
authors: Tadanori
authors: T
authors: Mayumi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D004770:Enterovirus / Q000235:genetics; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D007763:Lac Operon; D008545:Melanoma / Q000378:metabolism / Q000628:therapy*; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009336:Necrosis; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D039564:Integrin alphaV; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins; C047981:arginyl-glycyl-aspartic acid