Mutant NPM1 (NPM1c neoantigen), HLA-A*02:01-restricted

Class

Autologous TCR-T cell therapy

Pathway

T-cell receptor-mediated cytotoxicity against NPM1c-expressing leukemic cells

NPM1 (nucleophosmin 1) is a protein that normally resides in the nucleolus of the cell. A specific mutation in this gene, called NPM1c, is one of the most frequent genetic changes found in acute myeloid leukemia (AML). This mutation not only relocates the protein within the cell but also creates a short, abnormal peptide fragment. When this fragment is displayed on the leukemic cell surface by a particular human leukocyte antigen (HLA) molecule, HLA-A*02:01, it forms a distinctive marker—called a neoantigen—that is unique to the cancer cell and absent from healthy tissue. Autologous TCR-T cell therapy exploits this by taking a patient's own T cells, engineering them to carry a T-cell receptor (TCR) that specifically recognizes this mutant peptide-HLA combination, expanding them outside the body, and reinfusing them. The engineered T cells then seek out and destroy leukemic cells presenting the mutant antigen while sparing normal cells that lack it. This strategy is relevant to AML treatment broadly, offering a way to redirect the immune system against a leukemia-defining mutation, though it depends on the patient carrying both the NPM1c mutation and the matching HLA-A*02:01 tissue type.