Cathepsin G peptide-HLA-A*02:01 complex (CTSG-HLA-A2)

The Cathepsin G peptide-HLA-A*02:01 complex is a prominent immunotherapy target in the treatment of myeloid leukemias. Cathepsin G (CTSG) is a serine protease found in the azurophilic granules of neutrophils; however, its expression is significantly upregulated in acute myeloid leukemia (AML) blasts and leukemic stem cells (UniProt P08311). Specific peptides derived from Cathepsin G, most notably the CG1 peptide (WLPVVGLSP), are processed and presented on the cell surface by HLA-A*02:01 molecules (Blood. 2000;95(5):1741-1749). This presentation allows the immune system to distinguish malignant myeloid cells from non-hematopoietic tissues. Therapeutic approaches targeting this complex include T-cell receptor (TCR) engineered T-cells and multi-antigen-targeted products like NEXI-001, which aim to induce T-cell mediated cytotoxicity against the tumor (Mol Ther. 2016;24(11):1970-1980). While effective, these therapies carry a risk of off-tumor/on-target toxicity, potentially leading to transient neutropenia due to the expression of Cathepsin G in normal developing myeloid cells.

Other names

CG1-HLA-A2 complexCathepsin G-derived peptide-MHC complexCTSG-HLA complexCathepsin G antigen

T-cell mediated cytotoxicity