title: Evaluation of apoptogenic adenovirus type 5 oncolytic vectors in a Syrian hamster head and neck cancer model.
abstract: Human adenovirus (HAdV) vectors are intensely investigated for virotherapy of a wide variety of human cancers. Here, we have evaluated the effect of two apoptogenic HAdV5 vectors in an immunocompetent Syrian hamster animal model of head and neck cancer. We established two cell lines of hamster cheek pouch squamous cell carcinomas, induced by treatment with 9,10-dimethyl-1,2-benzanthracene. These cell lines, when infected with HAdV5 mutants lp11w and lp11w/Δ55 K (which are defective in the expression of either E1B-19 K alone or both E1B-19 K and E1B-55 K proteins) exhibited enhanced apoptotic and cytotoxic responses. The cheek pouch tumor cells transplanted either subcutaneously at the flanks or in the cheek pouches of hamsters readily formed tumors. Intratumoral administration of HAdV5-E1B mutants efficiently suppressed the growth of tumors at both sites. Histological examination of orthotopic tumors revealed reduced vascularity and the expression of the viral fiber antigen in virus-administered cheek pouch tumors. These tumors also exhibited increased caspase-3 levels, suggesting that virus-induced apoptosis may contribute to tumor growth suppression. Our results suggest that the apoptogenic HAdV5 vectors may have utility for the treatment of human head and neck cancers.
authors.affiliation: Institute for Molecular Virology Saint Louis University School of Medicine 1100 South Grand Blvd, St. Louis, MO 63104.
authors.forename: S
authors.initials: S
authors.lastname: Vijayalingam
authors.affiliation: Institute for Molecular Virology Saint Louis University School of Medicine 1100 South Grand Blvd, St. Louis, MO 63104.
authors.forename: Mohan
authors.initials: M
authors.lastname: Kuppusamy
authors.affiliation: Institute for Molecular Virology Saint Louis University School of Medicine 1100 South Grand Blvd, St. Louis, MO 63104.
authors.forename: T
authors.initials: T
authors.lastname: Subramanian
authors.affiliation: Department of Comparative Medicine Saint Louis University School of Medicine 1100 South Grand Blvd, St. Louis, MO 63104.
authors.forename: Frank F
authors.initials: FF
authors.lastname: Strebeck
authors.affiliation: Department of Comparative Medicine Saint Louis University School of Medicine 1100 South Grand Blvd, St. Louis, MO 63104.
authors.forename: Cheri L
authors.initials: CL
authors.lastname: West
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery Saint Louis University Cancer Center 3655 Vista Ave, West Pavilion, St. Louis, MO 63110.
authors.forename: Mark
authors.initials: M
authors.lastname: Varvares
authors.affiliation: Institute for Molecular Virology Saint Louis University School of Medicine 1100 South Grand Blvd, St. Louis, MO 63104.
authors.forename: G
authors.initials: G
authors.lastname: Chinnadurai
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D017501:Adenovirus E1B Proteins / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017501:Adenovirus E1B Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene; D053148:Caspase 3