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	Yuka Okada, Naoki Okada, Shinsaku Nakagawa, Hiroyuki Mizuguchi, Koichi Takahashi, Nobuyasu Mizuno, Takuya Fujita, Akira Yamamoto, Takao Hayakawa, Tadanori Mayumi
Journal	Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 93 Issue 4 Pg. 436-44 (Apr 2002) ISSN: 0910-5050 [Print] Japan
PMID	11985794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies, Monoclonal Integrin alphaV Oligopeptides Tumor Necrosis Factor-alpha Green Fluorescent Proteins arginyl-glycyl-aspartic acid
Topics	Adenoviridae (genetics) Animals Antibodies, Monoclonal (metabolism) Cell Line, Tumor Cricetinae Enterovirus (genetics) Flow Cytometry Gene Transfer Techniques Genetic Therapy (methods) Genetic Vectors Green Fluorescent Proteins (metabolism) HeLa Cells Humans Integrin alphaV (metabolism) Lac Operon Melanoma (metabolism, therapy) Melanoma, Experimental (therapy) Mice Mice, Inbred C57BL Mutation Necrosis Oligopeptides (chemistry, pharmacology) Polymerase Chain Reaction Protein Binding Reverse Transcriptase Polymerase Chain Reaction Time Factors Tumor Necrosis Factor-alpha (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!