CG1 as a possible immunotherapeutic target for AML and CML
Yan J, Shi C, Yang G, et al. T-cell Receptor Mimic CAR T Cells Targeting Cathepsin G Signal Peptide. Leukemia. 2025; (doi: 10.1038/s41375-025-02652-0).
Building on the success of their T-cell receptor-mimic antibody (TCR-m) targeting the signal peptide CG1, scientists applied a similar construct to the development of chimeric antigen receptor (CAR) T cells. Immunotherapy targets in myeloid malignancies have been elusive, but the science supports CG1 as a viable option for acute (AML) and chronic myeloid leukemia (CML). Derived from cathepsin G (CG), it is presented by HLA-A2 in both of these cancers. Early evidence shows that CG1/A2-directed CAR T cells exhibit robust killing of HLA-A2-positive AML and CML without disrupting normal bone marrow hematopoiesis. Based on the findings, the researchers believe clinical development of CG1/A2-CAR T cells for AML and CMS should advance.