PR1 peptide epitope from proteinase 3 and neutrophil elastase presented by HLA-A2 (PR1/HLA-A2)

The PR1 peptide epitope is a 9-amino acid sequence (VLQELNVTV) derived from the azurophil granule proteases proteinase 3 (PR3) and neutrophil elastase (NE) [4, 7, 9]. It is presented on the cell surface by the human leukocyte antigen HLA-A*0201 (HLA-A2) and serves as a prominent leukemia-associated antigen (LAA) in myeloid malignancies such as acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) [3, 5, 7]. While PR3 and NE are expressed in normal granulocytes, they are significantly overexpressed in leukemic blasts and stem cells, leading to a higher density of PR1/HLA-A2 complexes on malignant cells [1, 9]. This differential expression allows for the selective targeting of leukemia cells by the immune system [6, 9]. Therapeutic strategies targeting this epitope include PR1 peptide vaccines designed to elicit host cytotoxic T lymphocyte (CTL) responses, as well as T-cell receptor (TCR)-like monoclonal antibodies (e.g., 8F4/Hu8F4) and chimeric antigen receptor (CAR) T cells [3, 7, 12]. These therapies aim to induce direct lysis of leukemic cells through mechanisms such as complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) [1, 7]. Clinical trials have demonstrated that the induction of PR1-specific immunity correlates with clinical responses and molecular remissions in patients with myeloid leukemia [8, 10, 13]. Safety concerns include potential off-target effects on normal myeloid cells, although preclinical studies suggest a therapeutic window for selective leukemia targeting [2, 4, 6].

Other names

PR1 peptideVLQELNVTV peptidePR1/HLA-A2 complexPR1/HLA-A*0201 complexProteinase 3-derived PR1 peptideNeutrophil elastase-derived PR1 peptide

Induction of PR1-specific cytotoxic T lymphocytes (CTLs) via vaccination; antibody-mediated complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC); and CAR-T cell-mediated direct cell lysis.