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Chronic gene delivery of interferon-inducible protein 10 through replication-competent retrovirus vectors suppresses tumor growth

Cancer Gene Therapy volume 12, pages 900–912 (2005)Cite this article

Abstract

Sustained maintenance of therapeutic levels of angiostatic proteins in tumor tissues continues to represent a major challenge to antiangiogenesis therapy of cancer. In this study, we tested the hypothesis of utilizing gene transfer via replication-competent retroviral (RCR) vectors for chronic protein delivery. We now show that bioactive human interferon-inducible protein-10 (IP10) can be secreted from a variety of mammalian cells upon transduction with RCR vectors carrying the human IP10 gene. The production of IP10 from RCR-transduced cells could be maintained for at least three months in culture. The level and duration of IP10 expression in vivo was sufficient to inhibit growth of subcutaneous (s.c.) tumors as well as metastatic lesions in mice. This tumor inhibition was correlated to a marked reduction in tumor vascularization and mitotic activity. By conducting immunohistological studies, we have been able to show that IP10 vector-affected tumors evidenced elevated levels of IL-12p35 mRNA, with no sign of changes in the local inflammatory response, however, as determined by macrophage infiltration and the expression of proinflammatory cytokines. We are addressing the feasibility of using RCR vector-based gene therapy as a more convenient alternative tool to chronically deliver antiangiogenic proteins for cancer therapy.

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Acknowledgements

We are grateful to P Volkers for help with statistic analysis, C Coulibaly and R Plesker for help in animal handling, K Boller for expert microscopic imaging, and to J Medvedovska for excellent technical assistance. This work was supported by Grant 2002.067.1 of the Wilhelm-Sander-Stiftung to CJB and KC.

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Authors and Affiliations

  1. Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, 63225, Germany

    Yuansheng Sun, Carsten Finger, Klaus Cichutek & Christian J Buchholz

  2. Department of Immunology, Hospital Universitario Clinica Puerta de Hierro, Madrid, 28035, Spain

    Luis Alvarez-Vallina

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  1. Yuansheng Sun
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Correspondence to Christian J Buchholz.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website (http://www.nature.com/cgt)

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Sun, Y., Finger, C., Alvarez-Vallina, L. et al. Chronic gene delivery of interferon-inducible protein 10 through replication-competent retrovirus vectors suppresses tumor growth. Cancer Gene Ther 12, 900–912 (2005). https://doi.org/10.1038/sj.cgt.7700854

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