Cathepsin G–derived peptide presented by HLA-C*07:02 (CTSG/HLA-C*07:02)

The Cathepsin G–derived peptide presented by HLA-C*07:02 is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for T-cell-based immunotherapy in myeloid malignancies (Van der Heiden et al., 2016). Cathepsin G (CTSG) is a serine protease primarily found in the azurophilic granules of neutrophils, but it is also highly overexpressed in the leukemic blasts of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (UniProt P08311). The specific peptide fragment, identified as the sequence RPLARV, is processed intracellularly and presented on the cell surface by the HLA-C*07:02 allele, a common Class I MHC molecule. This pMHC complex is recognized by high-affinity T-cell receptors (TCRs), which can be engineered into patient or donor T cells to induce a targeted graft-versus-leukemia (GvL) effect. Because CTSG is also expressed in healthy myeloid cells, the primary safety concern is the potential for transient or prolonged neutropenia and myelosuppression. However, this target is considered highly promising for treating relapsed AML after hematopoietic stem cell transplantation, where the elimination of the recipient's myeloid system is often a managed part of the therapeutic process.

Other names

CTSG-derived peptide/HLA-C*07:02 complexCathepsin G peptide-MHC complexRPLARV/HLA-C*07:02 complexMinor histocompatibility antigen CTSG

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex on the surface of leukemic cells, leading to T-cell activation, secretion of cytotoxic granules (perforin and granzyme), and targeted cell lysis (Van der Heiden et al., 2016).