Proteinase 3-derived PR1 peptide (PR1)

The Proteinase 3-derived PR1 peptide is a 9-amino acid HLA-A*0201-restricted epitope (VLQELNVTV) derived from the myeloid primary granule proteins proteinase 3 (PR3) and myeloperoxidase (MPO) (Molldrem et al., 2000). It is classified as a leukemia-associated antigen (LAA) because it is overexpressed on the surface of malignant myeloid cells, including those in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), compared to normal hematopoietic cells (Sergeeva et al., 2011). This differential expression allows the immune system to distinguish between cancerous and healthy cells. Therapeutic strategies targeting the PR1 epitope include peptide vaccines, T-cell receptor (TCR)-like monoclonal antibodies such as h8F4, and chimeric antigen receptor (CAR) T-cell therapies (Ma et al., 2016). These treatments aim to induce or provide a cytotoxic T lymphocyte (CTL) response that specifically lyses PR1-presenting tumor cells. While clinical trials have shown that PR1-specific immunity correlates with molecular remission, potential safety concerns include off-target effects on normal neutrophils and their precursors, which also express the parent proteins (Alatrash et al., 2010).

Other names

PR1 epitopeVLQELNVTV peptideProteinase 3 (169-177) peptidePR3-derived PR1 peptide

Stimulation of cytotoxic T lymphocyte (CTL) responses or direct binding of TCR-like antibodies to the HLA-A2/PR1 complex on the cell surface, leading to targeted lysis of leukemia cells.