Modification of tumor cells with Fas (CD95) antigen gene and Fas ligand (CD95L) gene transfection by electroporation for immunotherapy of cancer.
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.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000276:immunology / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D018274:Electroporation; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000235:genetics; D005839:Gentamicins / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods*; D007178:Inbreeding; D007271:Injections, Intradermal; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods; D019014:fas Receptor / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D005839:Gentamicins; D008562:Membrane Glycoproteins; D019014:fas Receptor; C010680:antibiotic G 418