Therapy of lung metastases through combined vaccination with carcinoma cells engineered to release IL-13 and IFN-γ

C. De Giovanni, G. Nicoletti, L. Landuzzi, I. Rossi, A. Astolfi, C. Ricci, E. Di Carlo, P. Musiani, G. Forni, D. Fradelizi, P. Nanni, P. L. Lollini

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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 languageEnglish
Pages (from-to)1698-1704
Number of pages7
JournalGene Therapy
Volume8
Issue number22
DOIs
Publication statusPublished - 2001

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Keywords

  • Engineered vaccine
  • Interferon-γ
  • Interleukin-13
  • Mammary carcinoma
  • Metastasis

ASJC Scopus subject areas

  • Genetics

Cite this

De Giovanni, C., Nicoletti, G., Landuzzi, L., Rossi, I., Astolfi, A., Ricci, C., Di Carlo, E., Musiani, P., Forni, G., Fradelizi, D., Nanni, P., & Lollini, P. L. (2001). Therapy of lung metastases through combined vaccination with carcinoma cells engineered to release IL-13 and IFN-γ. Gene Therapy, 8(22), 1698-1704. https://doi.org/10.1038/sj.gt.3301584