Abstract
TS/A spontaneous mouse mammary adenocarcinoma cells were engineered to release interferon-γ (IFN-γ), a Th1 cytokine (TS/A-IFNγ) and interleukin-13 (IL-13), a Th2 cytokine (TS/A-IL13). Mice bearing lung micrometastases induced by parental TS/A cells received repeated subcutaneous vaccinations with TS/A-IFNγ admixed with TS/A-IL13 engineered cells. This combined treatment cured up to 75% of mice, whereas vaccinations with either TS/A-IFNγ or TS/A-IL13 alone cured only 20-40% of mice. Combined TS/A-IL13 and TS/A-IFNγ therapeutic vaccinations elicited a reactive infiltrate of CD4+ and CD8+ lymphocytes in lung metastases and an increased production of IFN-γ in the spleen and lung, suggesting a shift of the immune response toward the Th1 type. The type of infiltrating cells along with the lack of efficacy in T cell-deficient mice point to a major role of T cells. In conclusion, no antagonism but a synergistic and effective definitive cure stems from the combined vaccination with tumor cells engineered to release a Th1 and a Th2 cytokine.
Original language | English |
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Pages (from-to) | 1698-1704 |
Number of pages | 7 |
Journal | Gene Therapy |
Volume | 8 |
Issue number | 22 |
DOIs | |
Publication status | Published - 2001 |
Keywords
- Engineered vaccine
- Interferon-γ
- Interleukin-13
- Mammary carcinoma
- Metastasis
ASJC Scopus subject areas
- Genetics