Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer

Xu Peng; Isaac Woodhouse; Gemma Hancock; Robert Parker; Kristina Marx; Julius Müller; Silvia Salatino; Thomas Partridge; Annalisa Nicastri; Hanqing Liao; Gary Kruppa; Karin Hellner; Lucy Dorrell; Nicola Ternette

doi:10.1016/j.isci.2023.106101

Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer

iScience. 2023 Feb 2;26(3):106101. doi: 10.1016/j.isci.2023.106101. eCollection 2023 Mar 17.

Authors

Xu Peng¹, Isaac Woodhouse¹, Gemma Hancock², Robert Parker^{1

3}, Kristina Marx⁴, Julius Müller³, Silvia Salatino⁵, Thomas Partridge², Annalisa Nicastri^{1

3}, Hanqing Liao^{1

3}, Gary Kruppa⁴, Karin Hellner⁶, Lucy Dorrell^{2

3

7}, Nicola Ternette^{1

3}

Affiliations

¹ Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, OX3 7DQ Oxford, UK.
² Nuffield Department of Medicine, University of Oxford, OX3 7FZ Oxford, UK.
³ The Jenner Institute, University of Oxford, OX3 7DQ Oxford, UK.
⁴ Bruker Daltonics, Fahrenheitstraße 4, 28359 Bremen, Germany.
⁵ Wellcome Centre Human Genetics, University of Oxford, OX3 7BN Oxford, UK.
⁶ Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, UK.
⁷ Immunocore Ltd., OX14 4RY Abingdon, UK.

Abstract

Current immunotherapeutic approaches for human papillomavirus (HPV)-driven cervical cancer target the viral oncogenes E6 and E7. We report viral canonical and alternative reading frame (ARF)-derived sequences presented on cervical tumor cells, including antigens encoded by the conserved viral gene E1. We confirm immunogenicity of the identified viral peptides in HPV-positive women, and women with cervical intraepithelial neoplasia. We observe consistent transcription of the E1, E6, and E7 genes in 10 primary cervical tumor resections from the four most common high-risk HPV subtypes (HPV16, 18, 31, and 45), suggesting the suitability of E1 as therapeutic target. We finally confirm HLA presentation of canonical peptides derived from E6 and E7, and ARF-derived viral peptides from a reverse-strand transcript spanning the HPV E1 and E2 genes in primary human cervical tumor tissue. Our results extend currently known viral immunotherapeutic targets in cervical cancer and highlight E1 as an important cervical cancer antigen.

Keywords: Cancer; Cell biology; Immunology.

Abstract

Grants and funding