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Title:
Identification of tumor antigens with immunopeptidomics | Nature Biotechnology
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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. Chong et al. review how the integration of mass spectrometry with proteogenomic approaches can identify noncanonical antigens.
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nature portfolio journals ny-eso-1–reactive t-cell receptor permissions reprints privacy policy nature portfolio advanced bioinformatics solutions george coukos & michal bassani-sternberg ny-eso-1–specific tcr–engineered cancer research advertising author information authors social media mass-spectrometry-based immunopeptidomics mass spectrometry-based identification multi-omic data analysis target-decoy search strategy mass spectrometry-based proteomics alternative tumour-specific antigens proteasome-catalyzed peptide cis-splicing author correspondence michal bassani-sternberg noncanonical antigen-processing mechanisms mhc-bound peptide epitopes peptide-signal amplification strategy shared tumor-specific antigens targetable tumor-specific antigens large-scale protein identifications mono-allelic cells enables cell-based cancer immunotherapy canonical reading frames data-independent acquisition proteomics neoepitope-driven tumor rejection cd8+ t-cell immunity annotated protein-coding genes trans-spliced peptide ligands trans-spliced peptide ligands ribosome profiling data making t-cell products nature+ nature 543 nature 427 nature 451 nature 547 nature 564 nature 565 nature post-translationally spliced peptides de novo sequencing post-translational modification analysis noncanonical antigens—antigens derived
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