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Inhibition of angiogenesis by a Semliki Forest virus vector expressing VEGFR-2 reduces tumour growth and metastasis in mice

Gene Therapy volume 14, pages 503–513 (2007)Cite this article

Abstract

Inhibition of tumour angiogenesis has been shown to restrict primary tumour growth and metastatic spread. This study examines the active induction of immune responses against tumour endothelial cells following immunization with recombinant Semliki Forest virus (rSFV) particles encoding murine vascular endothelial growth factor receptor-2 (VEGFR-2). This approach was tested in two murine tumour models, CT26 colon carcinoma and 4T1 metastasizing mammary carcinoma. Tumour growth and metastatic spread were shown to be significantly inhibited in mice that were prophylactically vaccinated or therapeutically treated with rSFV particles coding for VEGFR-2. Microvessel density analysis showed that immunization with rSFV led to significant inhibition of tumour angiogenesis. Therapeutic efficacy was found to be associated with the induction of an antibody response against VEGFR-2. Co-immunization of mice with rSFV particles encoding VEGFR-2 and interleukin (IL)-12 completely abrogated both the antibody response and the antitumour effect. However, co-immunization of mice with VEGFR-2 and IL-4 encoding particles was shown both to induce higher titres of anti-VEGFR-2 antibodies and lead to enhanced survival following tumour challenge when compared to mice vaccinated with VEGFR-2 particles alone. These findings indicate that active immunization with rSFV particles coding for VEGFR-2 can break immunological tolerance and could potentially be used as part of a novel treatment for cancer.

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Acknowledgements

We thank Alex Whelan for assistance with histopathological studies, Dorothy Mooney for help with laboratory protocols, Maureen McCullough for assistance with haematology and Brian Cloak who assisted with photomicrography. The work was supported by the European Union Fifth Framework Programme and Science Foundation Ireland.

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Authors and Affiliations

  1. UCD School of Agriculture, Food Science and Veterinary Medicine, Veterinary Sciences Centre, University College Dublin, Belfield, Dublin, Ireland

    J A Lyons, B J Sheahan & S E Galbraith

  2. Department of Microbiology, Virus Group, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin, Ireland

    S E Galbraith, G J Atkins & M N Fleeton

  3. Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, India

    R Mehra

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  1. J A Lyons
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  2. B J Sheahan
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Correspondence to G J Atkins.

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Lyons, J., Sheahan, B., Galbraith, S. et al. Inhibition of angiogenesis by a Semliki Forest virus vector expressing VEGFR-2 reduces tumour growth and metastasis in mice. Gene Ther 14, 503–513 (2007). https://doi.org/10.1038/sj.gt.3302889

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  • DOI: https://doi.org/10.1038/sj.gt.3302889

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