56 Identification and Prioritization of Human Endogenous Retrovirus–Derived Antigens for mRNA Vaccine Development in Renal Cell Carcinoma

Q: What does this research mean for the field?

An integrative framework identifies translated human endogenous retrovirus (hERV)-derived antigens across renal cell carcinoma subtypes, and mRNA vaccination targeting these antigens elicits robust antigen-specific CD8+ T cell responses that outperform peptide vaccination. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

Frankie Scallo; Anasuya Dighe; Josephine Burdekin; Emily Chang; Deepak Poduval; Mohammad Shahbazy; Étienne Caron; Jeffrey Ishizuka; David Braun

doi:10.1093/oncolo/oyag312.057

September 1, 2026The OncologistOpen Access

56 Identification and Prioritization of Human Endogenous Retrovirus–Derived Antigens for mRNA Vaccine Development in Renal Cell Carcinoma

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Key Points

To identify and prioritize tumor-specific antigens derived from human endogenous retroviruses across renal cell carcinoma subtypes for public mRNA vaccine development.
Analyzed 3,173 putative hERV loci across TCGA pan-cancer datasets, scoring candidates for high tumor expression and minimal normal tissue expression across renal cell carcinoma subtypes.
Generated candidate open reading frames via six-frame translation, filtered them using polysome sequencing data from ccRCC cell lines, and predicted HLA-binding affinities using HLAthena and netMHCpan.
Constructed a multi-epitope hERV-targeting mRNA vaccine and tested antigen-specific CD8+ T cell responses in HLA-A11 transgenic mice compared with peptide-based vaccination.
Identified ≥25 unique hERV candidates per RCC subtype, refining 294,927 initial open reading frames to 805 high-confidence translated open reading frames across 18 unique hERV loci in clear cell RCC.
Immunopeptidomics reanalysis validated endogenous presentation of prioritized hERV peptides, and HLA binding algorithms identified >80 high-affinity binders for HLA-A*11 from individual loci.
Prophylactic mRNA vaccination in HLA-A11 mice produced approximately threefold and twofold higher frequencies of tetramer-positive CD8+ T cells in the spleen and lymph nodes, respectively, compared to peptide vaccination.

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Implication

Preclinical study reveals shared retrovirus-derived antigens and robust immunogenicity in mice, indicating new mRNA vaccine targets for renal cell carcinoma.

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Cite This Study

Scallo et al. (2026) studied this question.

synapsesocial.com/papers/6a993653636c6408cfa7f555 https://doi.org/10.1093/oncolo/oyag312.057

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56 Identification and Prioritization of Human Endogenous Retrovirus–Derived Antigens for mRNA Vaccine Development in Renal Cell Carcinoma

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56 Identification and Prioritization of Human Endogenous Retrovirus–Derived Antigens for mRNA Vaccine Development in Renal Cell Carcinoma

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