title: Herpes simplex virus thymidine kinase and granulocyte macrophage colony-stimulating factor combination gene therapy in a murine CT26 cell colon cancer model.
abstract: We evaluated the antitumor effects of combination gene therapy on CT26 mouse colon cancer cells, using the genes for herpes simplex virus thymidine kinase gene HSV-TK combined with granulocyte macrophage colony-stimulating factor (GM-CSF) compared with HSV-TK alone. Cells, unmodified or retrovirally transduced with HSV-TK or GM-CSF, were inoculated subcutaneously into syngeneic BALB/c mice in various combinations. HSV-TK and GM-CSF were also delivered using different routes (in separate cells vs doubly transfected single cells). Both HSV-TK (with i.p. ganciclovir - GCV - treatment) and GM-CSF genes had independent antitumor effects, and given together they caused significant reduction in tumor volumes compared with the HSV-TK gene alone (P < 0.001). Following GCV treatment, however, the treated/control ratios for tumor volumes were not different between tumors containing either HSV-TK alone or both genes (0.27 vs 0.25, respectively). Thus, the presence of GM-CSF did not increase the bystander effect of HSV-TK. Tumors receiving genes transferred in separate cells tended to be more consistently suppressed after GCV treatment than when both genes were transferred in the same cells, although this was not statistically significant. Thus, combination GM-CSF and HSV-TK gene therapy produced greater therapeutic efficacy than HSV-TK alone, but the bystander effect was not enhanced by GM-CSF.
authors.affiliation: Department of Internal Medicine, Chungbuk National University College of Medicine, Hungdok-Gu, Cheongju, Korea.
authors.forename: Ki Hyeong
authors.initials: KH
authors.lastname: Lee
authors.forename: Hainan
authors.initials: H
authors.lastname: Piao
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Son
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
authors.forename: Noe Kyeong
authors.initials: NK
authors.lastname: Kim
authors.forename: Seung Taik
authors.initials: ST
authors.lastname: Kim
mesh_terms: D000818:Animals; D024201:Bystander Effect; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012190:Retroviridae / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013937:Thymidine Kinase