Interleukin-12 genetic administration suppressed metastatic liver tumor unsusceptible to CTL.
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.
Itokawa
Yoshiki
Y
Department of Digestive Surgery, Kyoto Prefectural University of Medicine, 602-8566, Kyoto, Japan.
Mazda
Osam
O
Ueda
Yuji
Y
Kishida
Tsunao
T
Asada
Hidetsugu
H
Cui
Feng De
FD
Fuji
Nobuaki
N
Fujiwara
Hitoshi
H
Shin-Ya
Masaharu
M
Yasutomi
Kakei
K
Imanishi
Jiro
J
Yamagishi
Hisakazu
H
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*
D018664:Interleukin-12