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The immune response elicited by mammary adenocarcinoma cells transduced with interferon-gamma and cytosine deaminase genes cures lung metastases by parental cells

Authors :
Flavia Frabetti
Patrizia Nanni
Guido Forni
Federica Cavallo
Mirella Giovarelli
Giordano Nicoletti
P.-L. Lollini
Lorena Landuzzi
Piero Musiani
C. De Giovanni
Ilaria Rossi
E. Di Carlo
Source :
Human gene therapy. 9(2)
Publication Year :
1998

Abstract

The parental cells of the TSA murine mammary adenocarcinoma (TSA-pc) were transfected with both the interferon-gamma (IFN-y) 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-y clones) was inhibited by a marked recruitment of granulocytes and macrophages. In mice harboring TSA-pc micrometastases, therapeutic vaccination with either IFN-gamma or CD single transfectants reduced the number of lung nodules, whereas CD-gamma 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-gamma 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-gamma cells was uneffective.

Details

ISSN :
10430342
Volume :
9
Issue :
2
Database :
OpenAIRE
Journal :
Human gene therapy
Accession number :
edsair.doi.dedup.....aa7ba192526b63532110411f9a9e508f