Cathepsin G peptide (CG1) presented by Human leukocyte antigen A*02:01 (CG1/HLA-A*02:01)

The CG1 peptide/HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) consisting of a 9-amino acid peptide (sequence: RLLMRKRPV) derived from the Cathepsin G protein, bound to the Human leukocyte antigen A*02:01 molecule (Heemskerk et al., 2003, Blood). Cathepsin G is a serine protease primarily found in the azurophilic granules of neutrophils but is significantly overexpressed in myeloid leukemia cells, such as those in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) (UniProt P08311). This overexpression makes the CG1/HLA-A*02:01 complex a viable target for T-cell-based immunotherapies, including T-cell receptor (TCR) engineered T-cells. Drugs targeting this complex, such as MDG1021, utilize high-affinity TCRs to recognize the pMHC on the surface of malignant cells, triggering a cytotoxic immune response (Medigene AG, 2021). The complex serves as a lineage-specific target because, while the protein is endogenous, its presentation level on malignant blasts is significantly higher than on most healthy tissues. However, because Cathepsin G is also expressed in healthy myeloid cells, therapeutic development must carefully manage potential off-tumor toxicities, such as transient neutropenia. Clinical trials have explored the safety and efficacy of TCR-T cells specific for this complex in patients with relapsed or refractory AML (ClinicalTrials.gov NCT04102436).

Other names

Cathepsin G (117-125) peptideRLLMRKRPV/HLA-A*02:01 complexCG1-HLA complexCathepsin G-derived peptide CG1

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