Mutant Nucleophosmin 1 peptide CLAVEEVSL presented by HLA-A*02:01 (NPM1-mut/HLA-A*02:01 complex)

Nucleophosmin 1 (NPM1) is a multifunctional nucleolar protein that is frequently mutated in acute myeloid leukemia (AML), occurring in approximately 30% of cases. Mutations typically involve a 4-base pair insertion in exon 12, which causes a frame-shift and generates a novel, highly immunogenic C-terminal sequence. The 9-mer peptide CLAVEEVSL is a neoantigen derived from this mutated sequence and is specifically presented on the cell surface by the HLA-A*02:01 major histocompatibility complex. Because this mutation is a shared or public neoantigen found across many patients and is absent in healthy tissues, the CLAVEEVSL/HLA-A*02:01 complex is an ideal target for T-cell receptor (TCR)-engineered T-cell therapies. Current therapeutic strategies involve the adoptive transfer of T cells modified with high-affinity TCRs, such as MB-dNPM1-TCR.1, that recognize this complex to induce targeted lysis of leukemic blasts while sparing normal hematopoietic stem cells.

Other names

NPM1mut-A0201CLAVEEVSL-HLA-A*02:01ΔNPM1-A2Mutant NPM1 neoantigenNPM1-mutated peptide-MHC complex

T-cell receptor (TCR) binding to the peptide-MHC complex, leading to T-cell mediated cytotoxicity against cells expressing the mutant NPM1 neoantigen.