Cathepsin G peptide (RLLMRTRGL) presented by HLA-A*0201 (CG1/HLA-A*0201)

The CG1 peptide presented by HLA-A*0201 is a tumor-associated antigen complex that serves as a target for immunotherapy in myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) (Heemskerk et al., Blood, 2003). The CG1 peptide is a 9-amino acid sequence (RLLMRTRGL) derived from Cathepsin G, a serine protease found in the azurophilic granules of neutrophils and their precursors (PubMed, PMID: 12689932). While Cathepsin G is a normal protein, it is significantly overexpressed in leukemic blasts, and its presentation by the common HLA-A*0201 MHC class I molecule makes it an attractive target for T-cell receptor (TCR)-based interventions (NexImmune, 2021). Drugs like NEXI-001 utilize T cells primed to recognize this specific pMHC complex to induce a targeted cytotoxic immune response against cancer cells (ClinicalTrials.gov, NCT04505813). A primary therapeutic challenge is the potential for on-target, off-tumor toxicity against healthy neutrophils, which also express Cathepsin G, potentially leading to transient neutropenia (Journal of Clinical Investigation, 2004). Despite this, the target remains a key component of multi-antigen strategies aimed at reducing leukemia relapse after hematopoietic stem cell transplantation.

Other names

CG1-HLA-A*0201RLLMRTRGL-HLA-A*02:01Cathepsin G peptide CG1CTSG peptide-HLA complexCathepsin G (9-17) peptide

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and targeted lysis of Cathepsin G-expressing cells.