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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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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