Combination gene therapy for salivary gland cancer.
An established combination gene therapy strategy involving adenovirus vector delivery of the herpes thymidine kinase (tk) and murine interleukin-2 genes was adapted to treat salivary gland cancer in a murine model. Salivary tumors were generated by transcutaneous injection of 5 x 10(5) murine squamous carcinoma cells into the submandibular gland of syngeneic C3H/HeJ mice. After one week, established submandibular gland tumors were injected with a recombinant adenovirus containing therapeutic and control genes. Animals were subsequently administered ganciclovir twice daily (25 mg/kg) for six days. All animals receiving tk and ganciclovir demonstrated tumor regression, however a significantly greater response was seen in mice that were treated with both tk + mIL-2. Residual tumors from all treatment and control groups were harvested for microscopic evaluation and immunohistochemistry staining. Specific immunostaining revealed a predominance of CD8+ lymphocytes in the tumor beds of the animals treated with IL-2, suggesting a preferential immune response resulting from the local IL-2 expression. Although still in its infancy, the concept or using adenoviral gene therapy strategies to provide less invasive means of treating salivary tumors is promising.
O'Malley
B W
BW
Department of Otolaryngology-HNS, Johns Hopkins University, Baltimore, Maryland 21203-6402, USA. bomalle@gwgate1.jhmi.jhu.edu
Li
D
D
D000256:Adenoviridae; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness; D012468:Salivary Gland Neoplasms / Q000473:pathology / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics
D007376:Interleukin-2; D013937:Thymidine Kinase