Y4A CAR T cells

Y4A CAR T cells are a specific variant of mesothelin (MSLN)-targeted chimeric antigen receptor T cells that utilize a VHH (variable domain of heavy chain-only antibody) binding domain. This variant was derived from the parental JZQ-B4 VHH CAR through a single-amino acid alanine substitution at the fourth residue (Y4A) of the complementarity-determining region 3 (CDR3). Although the Y4A mutation was intended to tune affinity, the resulting CAR still maintains high affinity (below 100 nM) for both human and mouse MSLN. In preclinical studies, Y4A CAR T cells failed to discriminate between cells with high and low antigen expression, leading to severe on-target, off-tumor toxicity and failure to control tumor growth in mesothelioma models. Consequently, Y4A is primarily utilized as a high-affinity research tool or control in studies focused on affinity-tuning strategies for solid tumors.

Other names

Y4A MSLN CAR T cellsY-4A MSLN CAR T cellsY 4A MSLN CAR T cellsY4A VHH CAR T cellsY-4A VHH CAR T cellsY 4A VHH CAR T cells