Nucleophosmin 1 W288fs frameshift neoantigen presented by HLA-A*02:01 (NPM1-mut/HLA-A*02:01)

The NPM1/W288fs peptide presented by HLA-A*02:01 is a tumor-specific neoantigen complex primarily associated with Acute Myeloid Leukemia (AML) (Falini et al., 2005, NEJM). Nucleophosmin 1 (NPM1) is a multifunctional protein that, when affected by the W288fs frameshift mutation, undergoes a C-terminal alteration and relocates from the nucleolus to the cytoplasm (van der Lee et al., 2019, Cancer Cell). This mutation creates a novel peptide sequence, such as CLAVEEVSL, which is processed and presented by the Major Histocompatibility Complex (MHC) class I molecule HLA-A*02:01 (Kloetzel et al., 2021, Blood). Since this neoantigen is exclusively expressed in leukemic cells and not in healthy tissues, it represents a high-value target for immunotherapy. Current therapeutic approaches include the development of T-cell receptor (TCR) engineered T-cells, such as MDG1011, and bispecific molecules designed to recognize this specific peptide-MHC complex (Medigene AG, 2023). These therapies aim to trigger a robust and selective immune response against AML blasts, potentially offering a curative option for patients with this genetic subtype while minimizing off-target effects.

Other names

NPM1c neoantigenCLAVEEVSL-HLA-A*02:01 complexNPM1 frameshift mutation peptideNPM1-mutant peptide-MHC complex

T-cell receptor (TCR) mediated recognition of the neoantigen-MHC complex leading to cytotoxic T-lymphocyte activation and tumor cell lysis.