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Therapeutic DNA Vaccine Against HPV16-Associated Cancer

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DNA Vaccines

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2197))

Abstract

Human papillomavirus (HPV) is a contagious cause of anogenital and oropharyngeal cancers developing from persistently infected and subsequently transformed basal keratinocytes of mucosal epithelium. DNA-based immunotherapy offers great potential for the treatment of persisting HPV infections and associated cancers. Preclinical testing of therapeutic DNA-based HPV-targeted immunotherapy requires robust animal models which mimic HPV-associated cancer disease in humans. Here we describe a detailed protocol of intradermal delivery of a therapeutic DNA vaccine and a grafting model of neoantigen expressing skin to evaluate vaccine efficacy against HPV16 mediated hyperproliferative epithelium in mice.

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References

  1. Graham SV (2017) The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review. Clin Sci 131(17):2201–2221

    Article  CAS  Google Scholar 

  2. Walboomers JMM, Jacobs MV, Manos MM et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19

    Article  CAS  Google Scholar 

  3. Frazer IH (2014) Development and implementation of papillomavirus prophylactic vaccines. J Immunol 192:4007–4011

    Article  CAS  Google Scholar 

  4. Trimble CL, Peng S, Kos F et al (2009) A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res 15:361–367

    Article  CAS  Google Scholar 

  5. Trimble CL, Morrow MP, Kraynyak KA et al (2015) Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet 386(10008):2078–2088

    Article  CAS  Google Scholar 

  6. Alvarez RD, Huh WK, Bae S et al (2016) A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+cervical intraepithelial neoplasia 2/3 (CIN2/3). Gynecol Oncol 140:245–252

    Article  CAS  Google Scholar 

  7. Kim TJ, Jin HT, Hur SY et al (2014) Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nat Commun 5:5317

    Article  CAS  Google Scholar 

  8. Chandra J, Dutton JL, Li B et al (2017) DNA vaccine encoding HPV16 oncogenes E6 and E7 induces potent cell-mediated and humoral immunity which protects in tumor challenge and drives E7-expressing skin graft rejection. J Immunother 40:62–70

    Article  CAS  Google Scholar 

  9. Lin KY, Guarnieri FG, StaveleyOCarroll KF et al (1996) Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 56:21–26

    CAS  PubMed  Google Scholar 

  10. Hung CF, Wu TC, Monie A et al (2008) Antigen-specific immunotherapy of cervical and ovarian cancer. Immunol Rev 222:43–69

    Article  CAS  Google Scholar 

  11. Herber R, Liem A, Pitot H et al (1996) Squamous epithelial hyperplasia and carcinoma in mice transgenic for the human papillomavirus type 16 E7 oncogene. J Virol 70:1873–1881

    Article  CAS  Google Scholar 

  12. Tuong ZK, Noske K, Kuo P et al (2018) Murine HPV16 E7-expressing transgenic skin effectively emulates the cellular and molecular features of human high-grade squamous intraepithelial lesions. Papillomavirus Res 5:6–20

    Article  CAS  Google Scholar 

  13. Jazayeri SD, Kuo PT, Leggatt GR et al (2017) HPV16-E7-specific activated CD8 T cells in E7 transgenic skin and skin grafts. Front Immunol 8:524

    Article  Google Scholar 

  14. Bergot AS, Ford N, Leggatt GR et al (2014) HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2-and CCL5-mediated recruitment of mast cells. PLoS Pathog 10(10):e1004466

    Article  Google Scholar 

  15. Mattarollo SR, Frazer IH (2012) Response to comment on “Invariant NKT cells in hyperplastic skin induced a local immune suppressive environment by IFN-gamma production”. J Immunol 188(3):931–932

    Article  CAS  Google Scholar 

  16. Gosmann C, Mattarollo SR, Bridge JA et al (2014) IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia. J Immunol 193:2248–2257

    Article  CAS  Google Scholar 

  17. Matsumoto K, Leggatt GR, Zhong J et al (2004) Impaired antigen presentation and effectiveness of combined active/passive immunotherapy for epithelial tumors. J Natl Cancer Inst 96:1611–1619

    Article  CAS  Google Scholar 

  18. Narayan S, Choyce A, Linedale R et al (2009) Epithelial expression of human papillomavirus type 16 E7 protein results in peripheral CD8 T-cell suppression mediated by CD4+CD25+ T cells. Eur J Immunol 39:481–490

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1124265) to M. Yu. We acknowledge TRI for providing the excellent research environment and core facilities that enabled this work. We particularly thank the Biological Resources Core Facility for excellent animal care and technical support.

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Correspondence to Janin Chandra .

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Yu, M., Chandra, J. (2021). Therapeutic DNA Vaccine Against HPV16-Associated Cancer. In: Sousa, Â. (eds) DNA Vaccines. Methods in Molecular Biology, vol 2197. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0872-2_13

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  • DOI: https://doi.org/10.1007/978-1-0716-0872-2_13

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0871-5

  • Online ISBN: 978-1-0716-0872-2

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