Gene transfer of Fas ligand induces tumor regression in vivo

Hiroshi Arai, David Gordon, Elizabeth G. Nabel, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

252 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13862-13867
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number25
DOIs
StatePublished - Dec 9 1997
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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