title: Interleukin-12 genetic administration suppressed metastatic liver tumor unsusceptible to CTL.
abstract: A cytokine gene therapy approach was conducted against metastatic lesions of cytotoxic T lymphocyte (CTL)-unsusceptible tumor in mice. The EBV-based and conventional plasmid vectors that encode murine interleukin-12 (IL-12) gene (pGEG.mIL-12 and pG.mIL-12, respectively) were intravenously transfected into the mice that had received a subcutaneous inoculation of M5076 sarcoma cells. The pGEG.mIL-12 transfection drastically suppressed the subcutaneous as well as hepatic metastatic tumors, resulting in significant prolongation of survival period of the animals. Although single administration with pG.mIL-12 was not effective, repetitive transfection with the plasmid significantly prolonged the longevity of the mice-bearing the metastatic liver tumors. Multiple transfection with either pGEG.mIL-12 or pG.mIL-12 also suppressed peritoneal carcinomatosis in mice that had been injected with M5076 cells into the peritoneal cavity. It was suggested that a high level IL-12 production elicited by the intravenous delivery of the cytokine gene may be quite effective in inhibiting metastatic and CTL-unsusceptible neoplasms.
authors.affiliation: Department of Digestive Surgery, Kyoto Prefectural University of Medicine, 602-8566, Kyoto, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Itokawa
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Asada
authors.forename: Feng De
authors.initials: FD
authors.lastname: Cui
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Fuji
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Shin-Ya
authors.forename: Kakei
authors.initials: K
authors.lastname: Yasutomi
authors.forename: Jiro
authors.initials: J
authors.lastname: Imanishi
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yamagishi
mesh_terms: D000818:Animals; D005260:Female; D015316:Genetic Therapy; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018664:Interleukin-12