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Retrovirus-mediated IL-4 gene therapy in spontaneous adenocarcinomas from MMTV-neu transgenic mice

Gene Therapy volume 6, pages 1893–1897 (1999)Cite this article

Abstract

Gene therapy approaches to the treatment of experimental cancer are usually based on established neoplastic cell lines which are manipulated in vitro and subsequently transplanted in host animals. However, the relevance of these artificial models to the biology and therapy of human tumors is uncertain. We have previously validated an experimental model based on MMTV-neu transgenic mice in which breast tumors arise spontaneously in 100% of animals and have many features in common with their human counterpart, including the involvement of the neu oncogene and the ability to metastatize. In this article we report the effect of intratumoral, retrovirus-mediated, IL-4 expression on the growth of breast tumors arising in these mice. The size of IL-4 inoculated tumors on the right side was significantly smaller than that of controlateral untreated tumors, suggesting a local effect of IL-4. In addition, the non-injected tumors on the left side of treated animals were significantly smaller than those arising in control transgenic mice, suggesting that IL-4 can also inhibit tumor growth systemically. These findings suggest that IL-4 gene transfer can significantly reduce the growth rate of spontaneously arising breast tumors and that immune-based gene therapy could efficiently complement other approaches based on different mechanisms, such as suicide gene transfer or antisense technology.

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Acknowledgements

The technical assistance of Dario Strina, Angela Pettinicchio and Remo Di Bacco is acknowledged. We thank Prof R Dulbecco for encouragement and Ms Victoria Starnes for typing the manuscript. The financial support of AIRC to AV is gratefully acknowledged. This is manuscript No. 28 of the Genoma 2000/ITBA Project funded by CARIPLO. SB is supported by a fellowship from AIRC.

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Authors and Affiliations

  1. Department of Human Genome and Multifactorial Diseases, Istituto di Tecnologie Biomediche Avanzate, CNR, Segrate (MI), Italy

    M G Sacco, E Mira Catò, A Villa & P Vezzoni

  2. Istituto Nazionale Neurologico C Besta, Milan, Italy

    S Benedetti, B Pirola & G Finocchiaro

  3. Istituto di Anatomia Patologica Veterinaria e Patologia aviare, University of Milan, Milan, Italy

    M Caniatti, R Ceruti & E Scanziani

Authors
  1. M G Sacco
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  2. S Benedetti
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  3. E Mira Catò
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  4. M Caniatti
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  5. R Ceruti
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  6. E Scanziani
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  8. A Villa
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  9. G Finocchiaro
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Sacco, M., Benedetti, S., Catò, E. et al. Retrovirus-mediated IL-4 gene therapy in spontaneous adenocarcinomas from MMTV-neu transgenic mice. Gene Ther 6, 1893–1897 (1999). https://doi.org/10.1038/sj.gt.3301017

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  • DOI: https://doi.org/10.1038/sj.gt.3301017

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