Gene transfer of Fas ligand induces tumor regression in vivo.
The Fas-Fas ligand (FasL) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. Herein, we report that gene transfer of FasL inhibits tumor cell growth in vivo. Although such inhibition is expected in Fas+ tumor cell lines, marked regression was unexpectedly observed after FasL gene transfer into the CT26 colon carcinoma that does not express Fas. Infection by an adenoviral vector encoding FasL rapidly eliminated tumor masses in the Fas+ Renca tumor by inducing cell death, whereas the elimination of Fas- CT26 cells was mediated by inflammatory cells. Analysis of human malignancies revealed Fas, but not FasL, expression in a majority of tumors and susceptibility to FasL in most Fas+ cell lines. These findings suggest that gene transfer of FasL generates apoptotic responses and induces potent inflammatory reactions that can be used to induce the regression of malignancies.
Arai
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Howard Hughes Medical Institute, University of Michigan Medical Center, 1150 West Medical Center Drive, 4520 MSRB I, Ann Arbor, MI 48109-0650, USA.
Gordon
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D
Nabel
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EG
Nabel
G J
GJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D053222:Fas Ligand Protein; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014185:Transplantation, Isogeneic; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor