Proteinase 3-derived peptide PR1 (PR1)

PR1 is a 9-amino acid peptide (VLQELNVTV) derived from the azurophilic granule proteins proteinase 3 (PR3) and myeloperoxidase (MPO), which are overexpressed in myeloid leukemia cells (Molldrem et al., Nature Medicine, 2000). It is a well-characterized leukemia-associated antigen (LAA) that is presented on the cell surface by the HLA-A*02:01 MHC class I molecule (Rezvani et al., Blood, 2008). In healthy individuals, PR3 and MPO are primarily sequestered in the granules of mature neutrophils, but in myeloid malignancies like acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), these proteins are aberrantly expressed and processed, leading to the presentation of PR1 (Alatrash et al., Journal of Immunotherapy, 2012). This differential presentation makes PR1 an attractive target for immunotherapy, as it allows the immune system to distinguish between malignant blasts and most normal tissues. Therapeutic approaches targeting PR1 include peptide vaccines designed to elicit a host cytotoxic T-lymphocyte (CTL) response, as well as adoptive T-cell therapies and TCR-like monoclonal antibodies, such as 8F4, that specifically bind the PR1/HLA-A2 complex (Sergeeva et al., Blood, 2011). Clinical studies have demonstrated that the presence of PR1-specific CTLs correlates with clinical remission and the 'graft-versus-leukemia' effect following allogeneic stem cell transplantation (Molldrem et al., Nature Medicine, 2000). Furthermore, the targeting of PR1 has shown potential in reducing minimal residual disease in patients with myeloid malignancies. Despite its promise, challenges remain, including the potential for off-target effects on normal myeloid precursors and the need for specific HLA-A2 matching in patients.

Other names

PR1 peptideVLQELNVTVPR3 (27-35) peptideProteinase 3 (27-35)MPO (577-585) peptide

The PR1 peptide acts as a leukemia-associated antigen that, when presented by HLA-A*02:01 molecules on the surface of malignant cells, serves as a target for cytotoxic T lymphocytes (CTLs) or TCR-like antibodies. Therapeutic strategies involve vaccinating patients to expand endogenous PR1-specific CTLs or using engineered T cells and antibodies to directly recognize and eliminate cells displaying the PR1/HLA-A2 complex (Molldrem et al., Nature Medicine, 2000; Sergeeva et al., Blood, 2011).