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A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects

Gene Therapy volume 13, pages 257–265 (2006)Cite this article

Abstract

Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancers. HPV E6 and E7 are two viral oncoproteins that are consistently expressed in HPV infections and HPV-associated malignancies. We have previously developed DNA vaccines encoding calreticulin (CRT) linked either to HPV type 16 (HPV-16) E6 or to HPV-16 E7, both of which generated significant antitumor effects against E6- and E7-expressing tumors. In this study, we demonstrate that simultaneous vaccination of C57BL/6 mice or HLA-A2 transgenic mice with both CRT/E6 and CRT/E7 DNA vaccines generates significant E6- and E7-specific T-cell immune responses in vaccinated mice. Furthermore, combined vaccination with both CRT/E6 and CRT/E7 DNA generates significantly better therapeutic antitumor effects against HPV E6- and E7-expressing tumors than vaccination with either CRT/E6 DNA or CRT/E7 DNA alone. Our data suggest that it may be desirable to combine DNA vaccines targeting E6 with DNA vaccines targeting E7 to develop effective immunotherapeutic strategies for control of HPV infection and HPV-associated lesions in a clinical setting.

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Acknowledgements

We thank Drs Drew M Pardoll, Robert J Kurman, and Richard Roden for helpful discussions. We would also like to thank Drs Ralph Hruban and Ken-Yu Lin for critical review of the manuscript. We thank Mr Bruno Macaes for the preparation of the manuscript. This work was supported by the National Cancer Institute.

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Authors and Affiliations

  1. Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

    S Peng, T T Tomson, L He, C-F Hung & T-C Wu

  2. Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

    C Trimble, C-F Hung & T-C Wu

  3. Department of Obstetrics and Gynecology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

    C Trimble & T-C Wu

  4. Department of Molecular Microbiology and Immunology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T-C Wu

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  1. S Peng
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Correspondence to T-C Wu.

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Peng, S., Tomson, T., Trimble, C. et al. A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects. Gene Ther 13, 257–265 (2006). https://doi.org/10.1038/sj.gt.3302646

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