Project description:Somatic mutations in cancer are a potential source of cancer specific neoantigens. Acute myeloid leukemia (AML) has common recurrent mutations shared between patients in addition to private mutations specific to individuals. We hypothesized that neoantigens derived from recurrent shared mutations would be attractive targets for future immunotherapy and sought to study the Class I and II HLA ligandomes of thirteen primary AML tumor samples and two AML cell lines (OCI-AML3 and MV4-11) using mass spectrometry. We identified two endogenous, mutation-bearing HLA Class I ligands from NPM1, which are predicted to bind the common HLA haplotypes, HLA-A*03:01 and HLA-A*02:01 respectively. We further derived CD8+ T cells from healthy donor peripheral blood samples which bound mutant-peptide loaded A*03:01 and A*02:01 tetramers, suggesting a new source of NPM1 mutation-specific T cell receptors (TCRs) for future evaluation. Since NPM1 is mutated in approximately one-third of patients with AML, the finding of endogenous NPM1 neoantigens supports future studies evaluating immunotherapeutic approaches against this target, for this subset of patients with AML.

2019-07-17 | PXD012083 | Pride

Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens.

Project description: Not available

| S-EPMC7160266 | biostudies-literature

An HLA-A*11:01-Binding Neoantigen from Mutated NPM1 as Target for TCR Gene Therapy in AML.

Project description: Not available

| S-EPMC8582585 | biostudies-literature

High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML.

Project description: Not available

| S-EPMC6265642 | biostudies-literature