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Identification of tumor antigens with immunopeptidomics
Abstract
The identification of actionable tumor antigens is indispensable for the development of several cancer immunotherapies, including T cell receptor-transduced T cells and patient-specific mRNA or peptide vaccines. Most known tumor antigens have been identified through extensive molecular characterization and are considered canonical if they derive from protein-coding regions of the genome. By eluting human leukocyte antigen-bound peptides from tumors and subjecting these to mass spectrometry analysis, the peptides can be identified by matching the resulting spectra against reference databases. Recently, mass-spectrometry-based immunopeptidomics has enabled the discovery of noncanonical antigens-antigens derived from sequences outside protein-coding regions or generated by noncanonical antigen-processing mechanisms. Coupled with transcriptomics and ribosome profiling, this method enables the identification of thousands of noncanonical peptides, of which a substantial fraction may be detected exclusively in tumors. Spectral matching against the immense noncanonical reference may generate false positives. However, sensitive mass spectrometry, analytical validation and advanced bioinformatics solutions are expected to uncover the full landscape of presented antigens and clinically relevant targets.
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Metadata
- Authors
- Chong, C., Coukos, G., & Bassani-Sternberg, M.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Venue
- Nature Biotechnology
- Published
- 2021-10-11
- Volume
- 40
- Issue
- 2
- Pages
- 175-188
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W3205542661
- Cited by
- 232
- References
- 10
- Citations by year
- 2026: 47 · 2025: 58 · 2024: 45 · 2023: 51 · 2022: 30 · 2021: 1
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- tumor antigens, immunopeptidomics, HLA-bound peptides, cancer immunotherapy, T cell receptor transduction, peptide vaccine, mRNA vaccines, ribosome profiling, spectral matching, false positives
- MeSH terms
- Antigens, Neoplasm, HLA Antigens, Humans, Neoplasms, Peptides, Mass Spectrometry, Histocompatibility Antigens Class I
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