Proteinase 3 and Neutrophil Elastase (PR3/NE)

Proteinase 3 (PR3), also known as myeloblastin, and Neutrophil Elastase (NE) are serine proteases primarily localized within the azurophilic granules of myeloid cells. In the context of oncology, they are recognized as leukemia-associated source antigens because they both contain the identical nonameric peptide sequence PR1 (VLQELNVTV). This peptide is processed and presented on the cell surface by HLA-A*02:01, making it a specific target for immunotherapy in myeloid malignancies such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). While these proteins are also expressed in normal neutrophils, their significant overexpression in leukemic blasts and stem cells provides a therapeutic window for targeted intervention. Current drug development efforts include PR1 peptide vaccines, TCR-like monoclonal antibodies (e.g., 8F4), and CAR-T cells designed to recognize the PR1/HLA-A2 complex. Clinical studies have demonstrated that targeting this complex can induce leukemia-specific immune responses with manageable toxicity, primarily correlating with improved event-free survival in patients with low disease burden.

Other names

PR1 antigenPR1 peptideMyeloblastinPRTN3ELANENeutrophil elastaseAzurophil granule proteases

Drugs targeting this complex primarily function through immunotherapy, including vaccine-induced activation of endogenous PR1-specific cytotoxic T lymphocytes (CTLs), adoptive transfer of ex vivo expanded PR1-CTLs, or the use of TCR-like monoclonal antibodies and CAR-T cells that recognize the PR1/HLA-A2 complex to mediate direct lysis of leukemic cells via complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).