Mutant nucleophosmin 1 peptide–HLA class I complex (HLA-A*02:01) (Mutant NPM1–HLA-A*02:01 (no widely accepted abbreviation; "NPM1" is commonly used for nucleophosmin 1, but the peptide-HLA complex itself has no standard abbreviation))

Mutant nucleophosmin 1 (NPM1) peptides resulting from common frameshift mutations in exon 12 generate a novel C-terminal neoepitope, most commonly the peptide CLAVEEVSL, which is presented on AML cell surfaces by HLA-A*02:01 molecules[1][3][5][7]. This complex acts as a leukemia-specific neoantigen recognized by cytotoxic CD8+ T cells, enabling development of immunotherapies such as TCR-engineered T cells and peptide vaccines. The target is considered ideal for immunotherapy because of its cancer specificity, immunogenicity, and prevalence in AML. The target is not a traditional receptor, enzyme, or channel, but a neoantigen peptide–MHC-I complex. Mutant NPM1 is a driver mutation in AML, present in about one-third of patients[1][3][9]. Immunotherapies (including TCR-T and peptide vaccines) are in development and clinical investigation for this target[1][3][5][7]. HLA-A*02:01 restriction limits the target population to those expressing this allele. No conventional drugs yet act on this target, but several cellular immunotherapies and vaccine strategies are under investigation[1][3][9].

Other names

NPM1 mutant peptide presented by HLA-A*02:01ΔNPM1–HLA-A*02:01 complexNPM1-mutated peptide–HLA-A2 complex

Targeted T-cell immune response (recognition and killing of AML cells displaying the mutant peptide–HLA complex via CD8+ T cells with engineered or naturally occurring TCRs)[1][3][5][7] Induction of specific cytotoxicity against AML cells expressing ΔNPM1 in HLA-A*02:01 context