Antitumor activity exhibited by Fas ligand (CD95L) overexpressed on lymphoid cells against Fas+ tumor cells.
Lymph node (LN) cells of Fas-mutant mice lpr/lpr (lpr) and lpr(cg)/lpr(cg) (lpr(cg)) express an increased level of Fas ligand (FasL) (CD95L). We examined the antitumor potential of cell-bound FasL on these LN cells against Fas+ tumor cells. Fas+ F6b and Fas- N1d cells were produced from murine hepatoma MH134 (Fas-) by gene transfection. lpr and lpr(cg) LN cells inhibited growth of F6b but not N1d cells in vitro. Neither gld/gld lpr/lpr (gld/lpr) LN cells, which lack both FasL and Fas, nor wild-type LN cells showed growth-inhibitory activities against F6b and N1d cells. The effector cells and molecule were CD4-CD8- T cells and FasL, respectively. The tumor neutralization test and adoptive transfer demonstrated that lpr and lpr(cg), but not gld/lpr, LN cells retarded the growth of F6b cells. Although anti-Fas antibody and FasL cause severe liver failure, wild-type mice injected with lpr LN cells appeared clinically normal. Adoptive transfer of lpr LN cells to F6b-bearing mice exerted the same antitumor activity in wild-type and gld/lpr recipient mice, indicating the applicability of cell-bound FasL for Fas-mediated target therapy of cancer. These results suggest that antitumor activity was dependent on the Fas-FasL system and that lymphoid cells overexpressing FasL can be powerful antitumor effector cells against Fas+ tumor cells.
Shimizu
M
M
Department of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan. shimizu@rinshoken.or.jp
Takeda
Y
Y
Yagita
H
H
Yoshimoto
T
T
Matsuzawa
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D053222:Fas Ligand Protein; D016219:Immunotherapy, Adoptive; D008113:Liver Neoplasms / Q000188:drug therapy; D008214:Lymphocytes / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000235:genetics; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor