Interleukin-12 genetic administration suppressed metastatic liver tumor unsusceptible to CTL

• Published in: Biochemical and biophysical research communications Vol. 314; no. 4; pp. 1072 - 1079
• Main Authors: Itokawa, Yoshiki, Mazda, Osam, Ueda, Yuji, Kishida, Tsunao, Asada, Hidetsugu, Cui, Feng-De, Fuji, Nobuaki, Fujiwara, Hitoshi, Shin-Ya, Masaharu, Yasutomi, Kakei, Imanishi, Jiro, Yamagishi, Hisakazu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.02.2004
• Subjects: Animals; Cytotoxic T lymphocytes; Epstein–Barr virus-based plasmid vector; Female; Gene therapy; Genetic Therapy; Hydrodynamics-based transfection; Interleukin-12; Interleukin-12 - administration & dosage; Interleukin-12 - genetics; Liver metastasis; Liver Neoplasms, Experimental - immunology; Liver Neoplasms, Experimental - pathology; Liver Neoplasms, Experimental - therapy; Mice; Mice, Inbred C57BL; Neoplasm Metastasis - immunology; Neoplasm Metastasis - prevention & control; Peritoneal carcinomatosis; T-Lymphocytes, Cytotoxic - immunology; Tumor; Interleukin-12; Peritoneal carcinomatosis; Epstein–Barr virus-based plasmid vector; Tumor; Hydrodynamics-based transfection; Gene therapy; Liver metastasis; Cytotoxic T lymphocytes
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.12.200

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.