title: A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model.
abstract: A therapeutic vaccine against minimal residual cancer cells is needed for the treatment of patients with colorectal cancer. Several gene therapy studies have revealed that the combination of a suicide gene and cytokine gene might induce effective antitumor immunity. In this study, we constructed an interleukin (IL)-18 and herpes simplex virus-thymidine kinase (HSV-TK) expression vector driven by the human telomerase reverse transcriptase (hTERT) promoter to study the efficacy of combination gene therapy with IL-18 and the HSV-TK suicide gene. Low immunogenic colon 26 cells were used for transfection and inoculation into syngeneic BALB/c mice. Large established tumors of colon 26 transfectants expressing IL-18 and HSV-TK driven by the hTERT promoter were completely eradicated after GCV administration in syngeneic BALB/c mice. Immunohistochemical analysis at the tumor rejection sites revealed enormous infiltrations of CD8+ T lymphocytes as well as CD4+ T lymphocytes and CD11b+ monocytes. Moreover, established distant tumors were completely eradicated by vaccination with the IL-18 and HSV-TK transfectants in combination with GCV. These data suggest that the IL-18 and suicide gene therapy can elicit antitumor specific immunity. In conclusion, gene therapy with IL-18 and HSV-TK plasmid vector driven by the hTERT promoter may be useful for cancer vaccination.
authors: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors: Kosuke
authors: K
authors: Higashi
authors: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors: Shoichi
authors: S
authors: Hazama
authors: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors: Atsuhiro
authors: A
authors: Araki
authors: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors: Kiyoshi
authors: K
authors: Yoshimura
authors: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors: Norio
authors: N
authors: Iizuka
authors: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors: Shigefumi
authors: S
authors: Yoshino
authors: Department of Molecular Biology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors: Takafumi
authors: T
authors: Noma
authors: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors: Masaaki
authors: M
authors: Oka
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000627:therapeutic use; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D020382:Interleukin-18 / Q000008:administration & dosage* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D011401:Promoter Regions, Genetic; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D019098:Telomerase / Q000235:genetics*; D013937:Thymidine Kinase / Q000008:administration & dosage* / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019496:Cancer Vaccines; D020382:Interleukin-18; D014764:Viral Proteins; D013937:Thymidine Kinase; C509186:TERT protein, human; D019098:Telomerase; D015774:Ganciclovir