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. 2017 May 2;35(19):2605-2611.
doi: 10.1016/j.vaccine.2017.03.025. Epub 2017 Apr 4.

Identification and characterization of enhancer agonist human cytotoxic T-cell epitopes of the human papillomavirus type 16 (HPV16) E6/E7

Kwong Y Tsang  1 , Massimo Fantini  1 , Romaine I Fernando  1 , Claudia Palena  1 , Justin M David  1 , James W Hodge  1 , Elizabeth S Gabitzsch  2 , Frank R Jones  2 , Jeffrey Schlom  3
Affiliations

Identification and characterization of enhancer agonist human cytotoxic T-cell epitopes of the human papillomavirus type 16 (HPV16) E6/E7

Kwong Y Tsang et al. Vaccine. .

Abstract

Human papillomavirus (HPV) is associated with the etiology of cervical carcinoma, head and neck squamous cell carcinoma, and several other cancer types. Vaccines directed against HPV virus-like particles and coat proteins have been extremely successful in the prevention of cervical cancer through the activation of host HPV-specific antibody responses; however, HPV-associated cancers remain a major public health problem. The development of a therapeutic vaccine will require the generation of T-cell responses directed against early HPV proteins (E6/E7) expressed in HPV-infected tumor cells. Clinical studies using various vaccine platforms have demonstrated that both HPV-specific human T cells can be generated and patient benefit can be achieved. However, no HPV therapeutic vaccine has been approved by the Food and Drug Administration to date. One method of enhancing the potential efficacy of a therapeutic vaccine is the generation of agonist epitopes. We report the first description of enhancer cytotoxic T lymphocyte agonist epitopes for HPV E6 and E7. While the in silico algorithm revealed six epitopes with potentially improved binding to human leukocyte antigen-A2 allele (HLA-A2)-Class I, 5/6 demonstrated enhanced binding to HLA-Class I in cell-based assays and only 3/6 had a greater ability to activate HPV-specific T cells which could lyse tumor cells expressing native HPV, compared to their native epitope counterparts. These agonist epitopes have potential for use in a range of HPV therapeutic vaccine platforms and for use in HPV-specific adoptive T- or natural killer-cell platforms.

Keywords: Agonist epitope; CTLs; E6; E7; HPV16.

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Conflict of interest statement

Conflicts of Interest

Laboratory of Tumor Immunology and Biology, NCI: C

Etubics Corporation: Elizabeth S. Gabitzsch is a shareholder and employee of Etubics and has stock options in the company. Frank R. Jones is a shareholder and employee of Etubics and has stock options in the company.

Figures

Fig. 1
Fig. 1
Binding of HPV16 E6 (a) and E7 (b) native and agonist peptides to HLA-A2 molecules. Peptides were analyzed for binding to T2A2 cell lines, as described in Materials and Methods. Peptides were used at various concentrations. MFI: mean fluorescence intensity
See this image and copyright information in PMC

References

    1. Syrjanen S. Human papillomavirus (HPV) in head and neck cancer. J Clin Virol. 2005;32(Suppl 1):S59–66. - PubMed
    1. Crum CP, McLachlin CM, Tate JE, Mutter GL. Pathobiology of vulvar squamous neoplasia. Curr Opin Obstet Gynecol. 1997;9:63–9. - PubMed
    1. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11:1048–56. - PubMed
    1. Guan P, Howell-Jones R, Li N, Bruni L, de Sanjose S, Franceschi S, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131:2349–59. - PubMed
    1. Hammarstedt L, Dahlstrand H, Lindquist D, Onelov L, Ryott M, Luo J, et al. The incidence of tonsillar cancer in Sweden is increasing. Acta Otolaryngol. 2007;127:988–92. - PubMed

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