Targeting of intracellular oncoproteins with peptide-centric CARs.

ABSTRACT: The majority of oncogenic drivers are intracellular proteins, 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 for generating 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 essential for tumorigenesis. We focused on targeting the unmutated peptide QYNPIRTTF discovered on HLA-A*24:02, which is derived from the neuroblastoma-dependency gene and maste

SUBMITTER: Yarmarkovich M 

PROVIDER: S-EPMC10665195 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature