Modification of Tumor Cells with Fas (CD95) Antigen Gene and Fas Ligand (CD95L) Gene Transfection by Electroporation for Immunotherapy of Cancer

Author： Shimizu Motomu Yoshimoto Takayuki Matsuzawa Akio Takeda Yasutaka

Publisher： Humana Press, Inc

ISSN： 1073-6085

Source： Molecular Biotechnology, Vol.25, Iss.1, 2003-09, pp. : 79-88

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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.