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 t ransplanted cells may cause graft rejection and, on the other hand, tumor c ells may lose their tumorigenicity when they are engineered to express FasL . These effects could be related to cytotoxic of neutrophils by Fast with a ctivation of their cytoxic study we investigated the antitumor effect of al logenic fibroblasts engineered to express Fast. Fibroblasts engineered to e xpress Fast (PA317/FasL) did not exert toxic effects on transformed liver c ell line (BNL) or colon cancer cell line (CT26) in vitro, but they could ab rogate their tumorigenicity in vivo. Histological examination the site of i mplantation of BNL cells mixed with PA317/FasL revealed massive infiltratio n 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 afte r priming resulted in protection of 100 or 50% of animals, respectively. Th is protective effect was due to CD8(+) cells since depletion of CD8(+) led to tumor formation.. in addition, treatment of pre-established BNL tumors w ith a subcutaneous injection of BNL and PA317/FasL cell mixture at a distan t site caused significant inhibition of tumor growth. These data demonstrat e that allogenic cells engineered with Fast are able to abolish tumor growt h and induce specific protective immunity when they are mixed with neoplast ic cells.