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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2000 Dec;91(12):1296–1302. doi: 10.1111/j.1349-7006.2000.tb00917.x

Synergistic Suppressive Effect of Double Transfection of Tumor Necrosis Factor‐α and Interleukin 12 Genes on Tumorigenicity of Meth‐A Cells

Hitoshi Fujiwara 1,2, Naofumi Yamauchi 1,3, Yasushi Sato 1, Katsunori Sasaki 1, Minoru Takahashi 1, Tetsuro Okamoto 1, Tsutomu Sato 1, Satoshi Iyama 1, Yoshikazu Koshita 4, Michiaki Hirayama 5, Hisakazu Yamagishi 2, Yoshiro Niitsu 1,✉
PMCID: PMC5926296  PMID: 11123429

Abstract

Tumor necrosis factor‐α(TNF‐α) and interleukin 12 (IL‐12), both potent antitumor cytokines, are known to be involved in the host's antitumor immune surveillance in tumor bearers, via different mechanisms. The former enhances the activities of dendritic cells, natural killer/lymphocyteactivated killer (NK/LAK) and cytotoxic T lymphocyte (CTL), while the latter induces Th1‐type cellular immunity and enhances the activities of natural killer T (NKT), NK/LAK and CTL. In the present study, in the expectation of synergistic actions of these cytokines in stimulating the host's immune responses, we investigated the feasibility of a cancer vaccine involving double transfection with both genes in a murine model. The expression of major histocompatibility complex (MHC) class I, class II and B7.1 on the surface of the double transfectants was enhanced as revealed by FACS analysis. A significant decrease in tumorigenicity was observed in mice inoculated with the double transfectants. Cytotoxicity assay revealed that the activities of NK/LAK and CTL from spleens of mice bearing the double transfectants were enhanced. The induction of tumor‐specific immunity was confirmed by rechallenge with parental Meth‐A cells in mice that had rejected the double transfectants. Thus, double transfection of TNF‐αand IL‐12 genes was considered to bring about synergistic suppressive effects on the tumorigenicity of transfectants through the activation of killer cells by produced cytokines and the enhancement of expression of MHC class I, II and B7.1 molecules.

Keywords: TNF‐α, IL‐12, MHC class I, B7.1, Cancer gene therapy

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