Endogenous viral elements constitute a complementary source of antigens for personalized cancer vaccines
Personalized cancer vaccines (PCVs) largely leverage neoantigens arising from somatic mutations, limiting their application to patients with relatively high tumor mutational burden (TMB). This underscores the need for alternative antigens to design PCVs for low TMB cancers. To this end, we substantiate endogenous retroviral elements (EVEs) as tumor antigens through large-scale genomic analyses of healthy tissues and solid cancers. These analyses revealed that the breadth of EVE expression in tumors stratify checkpoint inhibitor-treated melanoma patients into groups with differential overall and progression-free survival. To enable the design of PCVs containing EVE-derived epitopes with therapeutic potential, we developed a computational pipeline, ObsERV. We show that EVE-derived peptides are presented as epitopes on tumors and can be predicted by ObsERV. Preclinical testing of ObsERV demonstrates induction of sustained poly-functional CD4+ and CD8+ T-cell responses as well as long-term tumor protection. As such, EVEs may facilitate and improve PCVs, especially for low-TMB patients.
Authors
- Christian Garde
- Kirti Pandey (ORCID: https://orcid.org/0000-0003-0799-6376)
- Michail Angelos Pavlidis (ORCID: https://orcid.org/0000-0002-8942-8921)
- Thomas Trolle (ORCID: https://orcid.org/0000-0003-0762-2198)
- Sri H. Ramarathinam (ORCID: https://orcid.org/0000-0002-2787-1282)
- Mateo Sokač (ORCID: https://orcid.org/0000-0001-9896-1544)
- Emma J. Lange
- Shanzou Chung
- Pouya Faridi (ORCID: https://orcid.org/0000-0002-2712-3356)
- Johanne Ahrenfeldt (ORCID: https://orcid.org/0000-0001-9175-0373)
- Daniela Kleine‐Kohlbrecher
- Jens Vindahl Kringelum (ORCID: https://orcid.org/0000-0002-7415-3283)
- Pablo Garcés‐Velástegui (ORCID: https://orcid.org/0000-0002-2058-8193)
- Birgitte Rønø (ORCID: https://orcid.org/0009-0007-6197-2646)
- Nicolai J. Birkbak (ORCID: https://orcid.org/0000-0003-1613-9587)
- Anthony W. Purcell (ORCID: https://orcid.org/0000-0003-0532-8331)
- Stine Friis
Institutions
- Aarhus University (DK)
- Australian Regenerative Medicine Institute (AU)
- Aarhus University Hospital (DK)
- ExpreS2ion Biotechnologies (Denmark) (DK)
- Galaxy Biotech (United States) (US)
- Monash University (AU)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-03-20
- DOI
- https://doi.org/10.1038/s41541-025-01107-y
- Citations
- 4
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 3.19
Funders
- Aarhus Universitet
- Victorian Cancer Agency
- Aarhus Universitets Forskningsfond
- Lundbeckfonden
- IngaBritt och Arne Lundbergs Forskningsstiftelse
- Novo Nordisk
- Novo Nordisk Fonden
- H. Lundbeck A/S
- Medical Research Council
- National Health and Medical Research Council