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- Title
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.
- Authors
Asselin-Paturel, C; Lassau, N; Guinebretière, J-M; Zhang, J; Gay, F; Bex, F; Hallez, S; Leclere, J; Peronneau, P; Mami-Chouaib, F; Chouaib, S
- 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.
- Subjects
SEMLIKI Forest virus; GENETIC vectors; TUMORS; INTERLEUKIN-12; GENE therapy
- Publication
Gene Therapy, 1999, Vol 6, Issue 4, p606
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3300841