Systematic discovery of neoepitope-HLA pairs for neoantigens shared among patients and tumor types.

Journal

Nature biotechnology

ISSN: 1546-1696

Titre abrégé: Nat Biotechnol

Pays: United States

ID NLM: 9604648

Informations de publication

Date de publication:
19 Oct 2023

Historique:

received: 22 11 2022

accepted: 14 08 2023

medline: 20 10 2023

pubmed: 20 10 2023

entrez: 19 10 2023

Statut: aheadofprint

Résumé

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines. To evaluate the potential for immunogenicity, we identified T cell receptors that recognized select neoepitope-HLA pairs and elicited a response after introduction into human T cells. These cellular systems and our data on therapeutically relevant neoepitopes in their HLA contexts will aid researchers studying antigen processing as well as neoepitope targeting therapies.

Identifiants

DOI: 10.1038/s41587-023-01945-y PMID: 37857725

pubmed: 37857725

doi: 10.1038/s41587-023-01945-y

pii: 10.1038/s41587-023-01945-y

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

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