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Modification of tumor cells with Fas (CD95) antigen gene and Fas ligand (CD95L) gene transfection by electroporation for immunotherapy of cancer |
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| Authors: | Shimizu Motomu Yoshimoto Takayuki Matsuzawa Akio Takeda Yasutaka |
| Institution: | (1) Medical Research and Development Center, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Honkomagome 3-18-22, Bunkyo-ku, 113-8613 Tokyo, Japan;(2) Intractable Disease Research Center, Tokyo Medical University, Shinjuke 6-1-1, Shinjuku-ku, 160-8402 Tokyo;(3) Laboratory Animal Research Center, University of Tokyo, Shirokanedai 4-6-1, Miato-ku, 108-8639 Tokyo, Japan;(4) Department of Surgery, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Miato-ku, 108-8639 Tokyo, Japan |
| Abstract: | Electroporation is a method for introducing DNA into cells by using a high-voltage electric field. This method is very simple and easily manipulated. We describe here a method for the modification of tumor cells with the Fas/Apo-1 (CD95) antigen-gene and Fas ligand (FasL)-gene transfection through the use of electroporation, and suggest that the Fas-FasL system is a good target for the induction of apoptosis-mediated antitumor activity. The Fas receptor/ligand system induces apoptosis and plays an important role in regulation of the immune system. In the method described, hepatoma MH134 (Fas− and FasL−) is transfected with murine Fas and FasL cDNA. A single administration of monoclonal anti-Fas antibody efficiently suppresses the growth of F6b (MH134+Neo+Fas) tumors but not that of N1d (MH134+Neo) tumors in gld/gld lpr/lpr mice. MH134+Neo+FasL tumor cells were rejected after the induction of inflammation with infiltration of neutrophils in mice. These results suggest that electroporation and Fas-mediated apoptosis are a good method for inducing of antitumor activity. |
| Keywords: | Electroporation transfection Fas/Apo-1 CD95 Fas ligand monoclonal anti-Fas antibody apoptosis antitumor activity inflammation immunopotentiation cancer immunotherapy |
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