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

Summary: 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 vir...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223001785
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Summary:Summary: 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.
ISSN:2589-0042