Open AccessSynergistic Suppressive Effect of Double Transfection of Tumor Necrosis Factor‐α and Interleukin 12 Genes on Tumorigenicity of Meth‐A Cells
Author(s) -
Fujiwara Hitoshi,
Yamauchi Naofumi,
Sato Yasushi,
Sasaki Katsunori,
Takahashi Minoru,
Okamoto Tetsuro,
Sato Tsutomu,
Iyama Satoshi,
Koshita Yoshikazu,
Hirayama Michiaki,
Yamagishi Hisakazu,
Niitsu Yoshiro
Publication year - 2000
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2000.tb00917.x
Subject(s) - ctl* , tumor necrosis factor alpha , cytotoxic t cell , major histocompatibility complex , biology , transfection , lymphokine activated killer cell , immune system , mhc class i , natural killer cell , immunology , interleukin 12 , interleukin 2 , cellular immunity , cancer research , t cell , interleukin 21 , cell culture , in vitro , cd8 , genetics , biochemistry
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‐α and 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.