The parental cells of the TSA murine mammary adenocarcinoma (TSA-pc) were transfected with both the interferon-γ (IFN-γ) gene and the cytosine deaminase (CD) suicide gene to obtain a therapeutic vaccine active against TSA-pc lung metastases. Even in the absence of treatment with the prodrug 5-fluorocytosine (5-FC), the local growth of double transfectants (CD-γ clones) was inhibited by a marked recruitment of granulocytes and macrophages. In mice harboring TSA-pc micrometastases, therapeutic vaccination with either IFN-γ or CD single transfectants reduced the number of lung nodules, whereas CD-γ double transfectants abrogated metastasis growth in up to 80% of mice. Treatment of mice with 5-FC did not alter the curative efficacy of CD-γ double-transfectant cells. By contrast, in mice vaccinated with CD single-transfectant cells, 5-FC treatment caused a significant loss of their curative activity. Host T cells played an active role in the cure of lung metastases, because vaccination of nude mice with CD-γ cells was uneffective.
|Number of pages||8|
|Journal||Human Gene Therapy|
|Publication status||Published - Jan 20 1998|
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