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Evaluation of combined vaccinia virus–mediated antitumor gene therapy with p53, IL-2, and IL-12 in a glioma model

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Abstract

Our previous studies have shown that vaccinia virus (VV) expressing p53, interleukin-2 (IL-2), and interleukin-12 (IL-12) results in an effective inhibition of subcutaneous glioma growth in mice. We propose that combination therapy of tumors with virus-mediated p53 and cytokine genes offers the prospect of synergistic antitumor response. In this work, the antitumor efficacy of VV-mediated combination of p53, IL-2, and IL-12 genes was evaluated in a nude mouse model. To minimize cytokine-associated toxicity, a virus dose as low as 10 plaque-forming units of VV expressing IL-2 and IL-12 per animal was used alone and together with 2×107 plaque-forming units of VV expressing p53. Intratumoral treatment of established C6 glioma with recombinant viruses rVV-p53, rVV-mIL2, rVV-mIL12, and rVV-2-12 induced the prolonged expression of p53, IL-2, IL-12, and both cytokines simultaneously. The combination of rVV-p53/rVV-mIL12 or rVV-p53/rVV-2-12 resulted in significant tumor inhibition compared to single modality treatment (P<.05). rVV-p53/rVV-2-12 therapy was associated with significant elevation of natural killer, Mac-1+, and NKT cells in blood and interferon-γ and tumor necrosis factor-α expression in tumors. The difference in the inhibition of tumor growth between the rVV-p53/rVV-mIL2 combination and rVV-p53 was statistically insignificant. These data demonstrate that gene therapy based on VV-mediated combination of p53, IL-2, and IL-12 treatment may be a promising adjunctive strategy for glioma treatment. Cancer Gene Therapy (2000) 7, 1437–1447

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Correspondence to Istvan Fodor.

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Chen, B., Timiryasova, T., Andres, M. et al. Evaluation of combined vaccinia virus–mediated antitumor gene therapy with p53, IL-2, and IL-12 in a glioma model. Cancer Gene Ther 7, 1437–1447 (2000). https://doi.org/10.1038/sj.cgt.7700252

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  • DOI: https://doi.org/10.1038/sj.cgt.7700252

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