Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL)

Fas ligand is a type It transmembrane protein which can induce apoptosis in Fas-expressing cells. Recent reports indicate that expression of Fast in transplanted cells may cause graft rejection and, on the other hand, tumor cells may lose their tumorigenicity when they are engineered to express FasL. These effects could be related to cytotoxic of neutrophils by Fast with activation of their cytoxic study we investigated the antitumor effect of allogenic fibroblasts engineered to express Fast. Fibroblasts engineered to express Fast (PA317/FasL) did not exert toxic effects on transformed liver cell line (BNL) or colon cancer cell line (CT26) in vitro, but they could abrogate their tumorigenicity in vivo. Histological examination the site of implantation of BNL cells mixed with PA317/FasL revealed massive infiltration of polymorphonuclear neutrophils and mononuclear cells. A specific immune protective effect was observed in animals primed with a mixture of BNL or CT26 and PA317/FasL cells. Rechallenge with tumor cells 14 or 100 days after priming resulted in protection of 100 or 50% of animals, respectively. This protective effect was due to CD8(+) cells since depletion of CD8(+) led to tumor formation.. in addition, treatment of pre-established BNL tumors with a subcutaneous injection of BNL and PA317/FasL cell mixture at a distant site caused significant inhibition of tumor growth. These data demonstrate that allogenic cells engineered with Fast are able to abolish tumor growth and induce specific protective immunity when they are mixed with neoplastic cells.