THE IMMUNE-RESPONSE ELICITED BY MAMMARY ADENOCARCINOMA CELLS TRANSDUCED WITH INTERFERON-GAMMA AND CYTOSINE DEAMINASE GENES CURES LUNG METASTASES BY PARENTAL CELLS

The parental cells of the TSA murine mammary adenocarcinoma (TSA-pc) w ere transfected with both the interferon-gamma (IFN-gamma) gene and th e cytosine deaminase (CD) suicide gene to obtain a therapeutic vaccine active against TSA-pc lung metastases. Even in the absence of treatme nt with the prodrug 5-fluorocytosine (5-FC), the local growth of doubl e transfectants (CD-gamma clones) was inhibited by a marked recruitmen t of granulocytes and macrophages, In mice harboring TSA-pc micrometas tases, therapeutic vaccination with either IFN-gamma or CD single tran sfectants reduced the number of lung nodules, whereas CD-gamma double transfectants abrogated metastasis growth in up to 80% of mice, Treatm ent of mice with 5-FC did not alter the curative efficacy of CD-gamma double-transfectant cells, By contrast, in mice vaccinated with CD sin gle-transfectant cells, 5-FC treatment caused a significant loss of th eir curative activity, Host T cells played an active role in the cure of lung metastases, because vaccination of nude mice with CD-gamma cel ls was uneffective.