Proteinase 3-derived PR1 peptide-HLA-A*0201 complex (PR1/HLA-A*0201)

The Proteinase 3-derived PR1 peptide-HLA-A*0201 complex is a prominent leukemia-associated antigen (LAA) used in the development of targeted immunotherapies (Molldrem et al., 2000). The PR1 epitope is a nonamer peptide with the sequence VLQELNVTV, derived from the azurophilic granule proteins Proteinase 3 and Neutrophil Elastase (Rezvani et al., 2008). These proteins are significantly overexpressed in myeloid leukemia cells, such as those in Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), compared to healthy tissues. When this peptide is presented on the cell surface by the HLA-A*0201 MHC class I molecule, it becomes a target for the immune system. Therapeutic strategies targeting this complex include PR1 peptide vaccines, TCR-like monoclonal antibodies such as h8F4, and adoptive T-cell therapies (Sergeeva et al., 2011). These treatments aim to induce selective lysis of leukemia blasts through T-cell mediated cytotoxicity or antibody-dependent mechanisms. A primary safety concern involves on-target, off-tumor effects, as the source proteins are also expressed in normal mature neutrophils and their progenitors. Consequently, clinical monitoring for neutropenia and bone marrow suppression is essential during treatment.

Other names

PR1 peptidePR1-HLA-A2 complexPR1/A2VLQELNVTV-HLA-A*0201Proteinase 3 (169-177) epitope

Induction of cytotoxic T-lymphocyte (CTL) response or antibody-dependent cellular cytotoxicity (ADCC) specifically against cells presenting the PR1 peptide in the context of HLA-A*0201.