Nucleophosmin 1 mutation-derived neoepitope AIQDLCLAV presented by Human Leukocyte Antigen A*02:01 (NPM1c-HLA-A*02:01)

The NPM1c neoepitope AIQDLCLAV presented by Human Leukocyte Antigen A*02:01 is a tumor-specific antigen derived from the most common genetic alteration in acute myeloid leukemia (AML), occurring in approximately 30% of cases (Falini et al., 2005, Blood). The mutation involves a frameshift in exon 12 of the Nucleophosmin 1 (NPM1) gene, leading to a novel C-terminal peptide sequence that is processed and presented on the cell surface by the HLA-A*02:01 allele (van der Lee et al., 2019, Blood). This specific peptide, AIQDLCLAV, is highly immunogenic and absent in normal tissues, making it an attractive target for T-cell receptor (TCR) engineered T-cell therapies (Hofmans et al., 2021, Frontiers in Oncology). Several experimental TCR-T therapies and TCR-like antibodies are being developed to target this complex to provide a precision medicine approach for AML patients (Xie et al., 2021, Nature Communications). The primary therapeutic mechanism involves the recognition of the peptide-MHC complex by engineered T cells, leading to the selective lysis of leukemic blasts. Monitoring for NPM1 mutation status and HLA-A*02:01 expression is essential for patient selection in clinical trials (Schuurhuis et al., 2018, Blood).

Other names

NPM1c neoantigenAIQDLCLAV-HLA-A*02:01 complexMutated Nucleophosmin 1 peptide-MHC complexNPM1-mutant neoepitopeNPM1c-A2

T-cell receptor-mediated cytotoxicity targeting the peptide-MHC complex on leukemic cells