Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs.

ABSTRACT: The majority of oncogenic drivers are intracellular proteins, thus constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes¹. However, most cancers have a modest mutational burden that is insufficient to generate responses using neoantigen-based therapies^2,3. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks⁴. Here we show that the neuroblastoma immunopeptidome is enriched with peptides derived from proteins that are essential for tumourigenesis and focus on targeting the unmutated peptide QYNPIRTTF, discovered on HLA-A*24:02, which is derived from the neuroblastoma dependency gen

SUBMITTER: Yarmarkovich M 

PROVIDER: S-EPMC8599005 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature