Nucleophosmin 1 mutant A283-291 peptide presented by Human Leukocyte Antigen A*02:01 (NPM1mut-A283-291/HLA-A*02:01)

The NPM1mut A283-291 peptide presented by HLA-A*02:01 is a highly specific tumor neoantigen complex found in a significant subset of patients with acute myeloid leukemia (AML). Nucleophosmin 1 (NPM1) is a nucleolar protein that, when mutated via a characteristic 4-base pair insertion (Type A mutation), undergoes a frame-shift at its C-terminus. This mutation results in the export of the protein to the cytoplasm and the generation of a novel, leukemia-specific peptide sequence, typically AIQDLCLAV, which is processed and presented on the cell surface by the HLA-A*02:01 molecule. Because this peptide is entirely absent in healthy cells, it serves as an ideal target for immunotherapy, particularly T-cell receptor (TCR) engineered T-cell therapies. Several clinical and preclinical programs, such as MDG1011, focus on leveraging this target to induce potent and selective destruction of AML blasts while sparing normal hematopoietic stem cells. The therapeutic success of targeting this complex depends on the stable expression of both the mutated NPM1 protein and the specific HLA-A*02:01 allele in the patient's tumor cells.

Other names

NPM1mut peptide-MHC complexAIQDLCLAV-HLA-A*02:01 complexNPM1-mutated neoantigenNPM1c neoantigen

Recognition of the specific peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies, leading to the targeted lysis of leukemic cells expressing the mutated NPM1 protein.