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

Gene Therapy volume 8, pages 1698–1704 (2001)Cite this article

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.

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Acknowledgements

We thank Mrs Gabriella Madrigali for her invaluable help and Dr John Iliffe for careful review of the manuscript. This work was supported by the Italian Association for Cancer Research (AIRC), the Italian Ministry for the Universities and Scientific and Technological Research (MURST), and local funds from the University of Bologna. A Astolfi and C Ricci are holders of PhD fellowships; I Rossi is holder of a fellowship from University of Bologna.

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Authors and Affiliations

  1. Department of Experimental Pathology, Section of Cancer Research, University of Bologna, Italy

    C De Giovanni, I Rossi, A Astolfi, C Ricci & P-L Lollini

  2. Biotechnology Satellite Unit of Bologna, IST, Bologna, Italy

    G Nicoletti & L Landuzzi

  3. Department of Oncology and Neuroscience, ‘G D'Annunzio’ University, Chieti, Italy

    E Di Carlo & P Musiani

  4. Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

    G Forni

  5. INSERM U477, University of Paris 5, Cochin Hospital, Paris, France

    D Fradelizi

  6. Interdepartmental Centre for Cancer Research ‘G Prodi’, University of Bologna, Italy

    P Nanni

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  1. C De Giovanni
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  2. G Nicoletti
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  7. E Di Carlo
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  8. P Musiani
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  9. G Forni
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  10. D Fradelizi
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  11. P Nanni
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  12. P-L Lollini
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De Giovanni, C., Nicoletti, G., Landuzzi, L. et al. Therapy of lung metastases through combined vaccination with carcinoma cells engineered to release IL-13 and IFN-γ. Gene Ther 8, 1698–1704 (2001). https://doi.org/10.1038/sj.gt.3301584

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  • DOI: https://doi.org/10.1038/sj.gt.3301584

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