High-avidity cathepsin-G-specific CAR-T cells for the treatment of acute myeloid leukemia - PubMed
3 hours ago
- #CAR-T cells
- #Cathepsin-G
- #Acute Myeloid Leukemia
- Development of a CAR-T cell therapy specific for a myeloid-restricted peptide from cathepsin-G, presented on HLA-A*02:01, to target acute myeloid leukemia (AML).
- Engineering of CG1.CAR-T cells with increased functional avidity via co-expression of LCK and duplicated CD3ζ chain, enabling recognition of peptide at concentrations as low as 0.025 mM.
- Optimized CG1.CAR-T cells demonstrated anti-leukemia effects in vitro and in vivo using patient-derived xenograft models, without causing hematopoietic toxicity.
- Mechanistic studies revealed LCK overexpression in CG1.CAR-T cells led to mitochondrial-related transcriptional changes, increased mitochondrial mass, and improved respiratory capacity.
- The findings suggest CG1.CAR-T cells have clinical potential for treating AML while minimizing toxicity to normal myeloid cells.