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Transfer of the murine interleukin-12 gene in vivo by a Semliki Forest virus vector induces B16 tumor regression through inhibition of tumor blood vessel formation monitored by Doppler ultrasonography

Gene Therapy volume 6, pages 606–615 (1999)Cite this article

Abstract

To elucidate further the potential of a Semliki Forest virus (SFV) vector in vivo for gene therapy, we constructed a vector, SFV-IL12, to transfer murine IL-12 genes into tumors. A single intratumoral injection of established B16 murine melanoma with SFV-IL12 resulted in a significant inhibition of tumor growth, while injection with SFV-LacZ had no effect. This antitumoral activity correlated with an increase of IFNγ production, MIG and IP-10 mRNA expression, both at the tumor site and at the periphery. In contrast, no increase in CTL- or NK cell-mediated cytotoxic response could be detected, ruling out the involvement of T and NK cell cytotoxicity. To determine how the transfer of IL-12 genes induced tumor regression, the antiangiogenicactivity of SFV-IL12 was investigated using Doppler ultrasonography (DUS). SFV-IL12 inhibited in situ neovascularization within the tumor, without affecting the resistance index of pre-existing intratumoral blood flows. In addition, histological analysis of SFV-IL12-treated tumors showed massive tumor necrosis induced by SFV-IL12 treatment. These data indicate that SFV-IL12 inhibits tumor growth through its antiangiogenic activity, demonstrated for the first time in vivo by DUS, and suggest that the SFV vector may be a novel valuable tool in tumor gene transfer.

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Authors and Affiliations

  1. U487 INSERM, Institut Gustave-Roussy, Villejuif, France

    C Asselin-Paturel, N Lassau, F Gay, F Mami-Chouaib & S Chouaib

  2. Département d’Imagerie Médicale, Institut Gustave-Roussy, Villejuif, France

    N Lassau & J Leclere

  3. Département d’Anatomo-Pathologie, Institut Gustave-Roussy, Villejuif, France

    J-M Guinebretière

  4. Département de Biologie Moleculaire, Université Libre de Bruxelles, Belgium

    J Zhang, F Bex & S Hallez

  5. CNRS ESA 70.57, Université de Jussieu, Paris, France

    P Peronneau

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Asselin-Paturel, C., Lassau, N., Guinebretière, JM. et al. Transfer of the murine interleukin-12 gene in vivo by a Semliki Forest virus vector induces B16 tumor regression through inhibition of tumor blood vessel formation monitored by Doppler ultrasonography. Gene Ther 6, 606–615 (1999). https://doi.org/10.1038/sj.gt.3300841

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  • DOI: https://doi.org/10.1038/sj.gt.3300841

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