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Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector

Gene Therapy volume 12, pages 147–159 (2005)Cite this article

Abstract

To assess the potential of immune stimulation in combination with apoptosis induction by Semliki Forest virus (SFV) and its derived vector for tumour treatment, we have utilized the poorly immunogenic and rapidly growing K-BALB and CT26 murine tumour models. Both cell lines underwent apoptosis and expressed viral antigen when infected with the SFV4 strain of SFV, or recombinant SFV (rSFV) virus-like particles (VLPs) encoding the p62-6k viral structural proteins. VLPs were used to immunize groups of BALB/c and BALB/c nu/nu mice prior to subcutaneous tumour induction and treatment. Direct intratumoral injection of VLPs or SFV4 resulted in an immediate and intense inflammatory reaction in immunized groups that was not observed in naïve groups until day 5 of treatment, and was not observed in nu/nu groups. A significantly higher level of tumour growth inhibition was observed in immunocompetent groups than in athymic mice. For K-BALB tumours, SFV4 treated groups showed greater inhibition than that observed in VLP-treated groups, with immunization prior to treatment enhancing the overall antitumour effect and immune response. No significant difference was observed in CT26 tumours between VLP and SFV4-treated groups, but prior immunization considerably enhanced the antitumoural response. It is concluded that use of the inherent apoptosis-inducing capability of SFV or its vector, by perfusion in combination with immune stimulation, may have potential for the treatment of rapidly growing tumours.

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Acknowledgements

We thank Marie Moore and Alex Whelan for assistance with histopathological studies, and Dorothy Mooney for assistance with laboratory protocols. This work was supported by the Enterprise Ireland Advanced Technology Research Programme, Cancer Research Ireland and the European Union 5th Framework Programme.

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Authors and Affiliations

  1. Department of Microbiology, Moyne Institute, Trinity College, Dublin, 2, Ireland

    J W P Smyth, M N Fleeton & G J Atkins

  2. Department of Veterinary Pathology, Faculty of Veterinary Medicine, University College Dublin, Belfield, Dublin, 4, Ireland

    B J Sheahan

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  1. J W P Smyth
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  2. M N Fleeton
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  4. G J Atkins
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Smyth, J., Fleeton, M., Sheahan, B. et al. Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector. Gene Ther 12, 147–159 (2005). https://doi.org/10.1038/sj.gt.3302390

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