Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors.
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.
Shashkova
Elena V
EV
Institute of Agricultural Biotechnology, Moscow, Russia.
Cherenova
Lubov V
LV
Kazansky
Dmitry B
DB
Doronin
Konstantin
K
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D025681:Fowl adenovirus A / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008546:Melanoma, Experimental / Q000235:genetics / Q000628:therapy* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018139:Simplexvirus / Q000201:enzymology*; D012878:Skin Neoplasms / Q000235:genetics / Q000628:therapy / Q000821:virology; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase