N9A CAR T cells

N9A CAR T cells are an affinity-tuned chimeric antigen receptor (CAR) T-cell therapy designed to selectively target mesothelin (MSLN) in solid tumors. Developed by researchers at Weill Cornell Medicine and Houston Methodist Research Institute, these cells utilize a single-domain nanobody (VHH) binder derived from the JZQ-B4 clone, which was discovered through alpaca immunization. The 'N9A' designation refers to a specific alanine substitution at position 9 of the complementarity-determining region 3 (CDR3), which reduces the binding affinity for MSLN by approximately 500-fold (KD > 100 nM) compared to the parental high-affinity construct. This micromolar affinity allows the T cells to discriminate between high antigen density on tumor cells and low basal expression on normal mesothelial tissues, thereby mitigating the risk of lethal on-target, off-tumor toxicity. The CAR construct incorporates a CD28 costimulatory domain, a CD3ζ signaling domain, and a somatostatin receptor 2 (SSTR2) reporter gene for non-invasive PET/CT imaging of T-cell biodistribution.

Other names

anti-MSLN N9A CAR T cellsaffinity-tuned MSLN CAR T cellsJZQ-B4 N9A CAR T cellsJZQ-B-4 N9A CAR T cellsJZQ-B 4 N9A CAR T cells