Cathepsin G peptide CG1-HLA-A*0201 complex (CG1/HLA-A*0201)

The Cathepsin G–derived peptide presented by HLA-A*0201, specifically the CG1 peptide (sequence: FLLPTGAEA), is a highly specific leukemia-associated antigen (LAA) that serves as a target for advanced immunotherapies (Zhang et al., 2013). Cathepsin G is a serine protease normally sequestered in the azurophilic granules of neutrophils; however, in malignancies such as acute myeloid leukemia (AML), it is overexpressed and aberrantly processed, leading to the presentation of its leader sequence-derived peptide on the cell surface via HLA-A*0201 (Alatrash et al., 2017). This peptide-MHC (pMHC) complex is preferentially expressed on leukemic blasts and leukemia stem cells (LSCs) compared to healthy hematopoietic progenitor cells, providing a selective therapeutic window (Shi et al., 2025). Therapeutic approaches currently in development include TCR-mimic (TCRm) antibodies and bispecific T-cell engagers, such as CBX-250, which are designed to recognize the pMHC complex and trigger T-cell mediated destruction of the tumor cells (Crossbow Therapeutics, 2024). The target is particularly significant for its potential to address minimal residual disease and improve outcomes in patients with relapsed or refractory myeloid leukemias (Alatrash et al., 2020).

Other names

CG1 peptideFLLPTGAEA peptideCathepsin G leader sequence peptideCG1/HLA-A2 complexCathepsin G (10-18) peptideCTSG-derived peptide/HLA-A*0201

T-cell engagement and recruitment via TCR-mimicry (TCRm) to induce targeted cytotoxic lysis of cells presenting the CG1 peptide in the context of HLA-A*0201.