IFN-ALPHA-1 GENE-EXPRESSION INTO A METASTATIC MURINE ADENOCARCINOMA (TS A) RESULTS IN CD8(+) T-CELL-MEDIATED TUMOR REJECTION AND DEVELOPMENT OF ANTITUMOR IMMUNITY - COMPARATIVE-STUDIES WITH IFN-GAMMA-PRODUCINGTS/A-CELLS/

Cells from a spontaneous, invasive, and metastasizing mouse mammary ad enocarcinoma (TS/A-pc) were transfected with a retroviral vector conta ining the mouse IFN-alpha 1 gene. TS/A clones secreting varying amount s of IFN-alpha 1 were isolated and their tumorigenicity was evaluated after s.c. or i.v. injection into immunocompetent BALB/c mice. Almost all of the IFN-alpha-secreting TS/A clones failed to grow in a high pe rcentage of mice or formed small tumors after a long latency time, whe reas TS/A-pc or transfection control cells always grew into large s.c. tumors. Rejection was mainly mediated by CD8(+) T lymphocytes and par tially by polymorphonuclear cells, as demonstrated by selective immuno suppression experiments and histologic and ultrastructural data. After rejection, a significant portion of mice displayed an immune resistan ce to the subsequent challenge with TS/A-pc. When the metastatic abili ty of IFN-alpha-secreting clones was compared with that of previously characterized IFN-gamma-secreting TS/A clones, it was found that the e xpression of IFN-alpha into TS/A tumor cells resulted in a potent inhi bition of metastases formation, whereas IFN-gamma expression either di d not affect or even enhanced the metastatic behavior of TS/A cells. T hese results provide strong evidence for the usefulness of IFN-alpha-p roducing tumor cells for the development of gene therapy strategies an d vaccines against metastatic tumors.