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  • Acquired Diseases
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Genetic immunization against cervical carcinoma: induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7

Gene Therapy volume 7, pages 1859–1866 (2000)Cite this article

Abstract

Infection of genital epithelial cells with human papillomavirus (HPV) types 16 and 18 is closely associated with the development of cervical carcinoma. The transforming potential of these high-risk HPVs depends on the expression of the E6 and E7 early viral gene products. Since the expression of E6 and E7 is selectively maintained in premalignant and malignant cervical lesions these proteins are attractive candidates for immunotherapeutic and prophylactic strategies. This report describes the construction, characterization and the in vivo immunotherapeutic potential of recombinant Semliki Forest virus (SFV) expressing the HPV16 E6 and E7 proteins (SFV-E6E7). Western blot analysis and immunofluorescence staining demonstrated expression of E6 and E7 in BHK cells infected with SFV-E6E7. Immunization of mice with SFV-E6E7 resulted in an efficient in vivo priming of HPV-specific CTL activity. The induced CTL lysed murine tumor cells transformed with the HPV16 genome and EL4 cells loaded with an immunodominant class I-binding HPV E7 peptide. CTLs could reproducably be induced by immunization with three injections of as few as 105 infectious units of SFV-E6E7. Protection from tumor challenge was studied using the tumor cell line TC-1. Immunization with 5 × 106 SFV-E6E7 particles protected 40% of the mice from tumor challenge. These results indicate that E6E7 expression by the efficient and safe recombinant SFV system represents a promising strategy for immunotherapy or immunoprophylaxis of cervical carcinoma.

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Acknowledgements

We thank Dr P Liljeström and Dr C Melief and their co-workers for advice and stimulating discussions and B Dontje and J Wijbenga for expert technical assistance. Part of this work was supported by Inex Pharmaceuticals Corporation (Burnaby, BC, Canada) and the EU Biotechnology and Biomedicine and Health Programmes.

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  1. Department of Medical Microbiology, Molecular Virology Section, University of Groningen, A Deusinglaan 1, Groningen, 9713 AV, The Netherlands

    T Daemen, F Pries, L Bungener, M Kraak, J Regts & J Wilschut

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  1. T Daemen
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Daemen, T., Pries, F., Bungener, L. et al. Genetic immunization against cervical carcinoma: induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7. Gene Ther 7, 1859–1866 (2000). https://doi.org/10.1038/sj.gt.3301257

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