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Cancer Gene Ther ; 12(7): 617-26, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15761475

ABSTRACT

Avian adenovirus CELO is a novel adenovirus vector system with the advantages of efficient production, high virion stability, and the absence of crossreactivity with Ad5-neutralizing antibodies. In this study, we evaluated the anticancer efficacy of a CELO vector encoding the herpes simplex virus type 1 thymidine kinase, a prodrug-activating therapeutic gene. Vectors carrying the gene for HSV-tk or EGFP under the control of the HCMV promoter in place of the "nonessential" region of the CELO genome were constructed. Anticancer activity of the CELO-TK vector was studied in vitro, in human and murine tumor cells in cell culture, and in vivo, in established subcutaneous murine B16 melanoma tumors in C57BL/6 mice. The CELO-TK vector mediated delivery of functional HSV-tk to tumor cell lines in cell culture. Comparison of the CELO-TK vector to a first-generation human adenovirus type 5 vector Ad5-TK in cultured H1299 cells showed equal levels of functional activity at increasing multiplicities of infection with CELO-based vector. CELO vectors allowed for transduction and expression of EGFP and HSV-tk genes in subcutaneous melanoma tumors in C57BL/6 mice. Intratumoral injections of CELO-TK followed by ganciclovir administration resulted in suppression of tumor growth and significantly increased the median of survival. The results of the study demonstrated the efficacy of CELO vector as a vehicle for the delivery of prodrug-activating genes such as HSV-tk to tumor cells in vitro and in vivo.


Subject(s)
Fowl adenovirus A/genetics , Genetic Therapy , Genetic Vectors , Melanoma, Experimental/therapy , Simplexvirus/enzymology , Thymidine Kinase/genetics , Animals , Cell Line, Tumor , Female , Green Fluorescent Proteins/genetics , Humans , Melanoma, Experimental/genetics , Melanoma, Experimental/virology , Mice , Mice, Inbred C57BL , Skin Neoplasms/genetics , Skin Neoplasms/therapy , Skin Neoplasms/virology , Transduction, Genetic , Xenograft Model Antitumor Assays
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