R3A CAR T cells

R3A CAR T cells are an experimental cellular immunotherapy consisting of T cells engineered to express a chimeric antigen receptor (CAR) targeting Mesothelin (MSLN). The CAR binder is a single-domain nanobody (VHH) derived from the JZQ-B4 clone, specifically modified with an alanine substitution at the third residue of the complementarity-determining region 3 (CDR3). Developed by researchers at Weill Cornell Medicine and Houston Methodist Research Institute, this construct was designed as part of an affinity-tuning study to evaluate the relationship between CAR affinity and on-target, off-tumor toxicity. R3A CAR T cells possess high affinity (equilibrium dissociation constant < 100 nM) for both human and mouse MSLN. In preclinical mouse models, the R3A variant exhibited potent systemic expansion and significant off-tumor infiltration into organs such as the lungs and liver, leading to fatal on-target, off-tumor toxicity. The construct incorporates CD28 and CD3ζ signaling domains and co-expresses the human somatostatin receptor 2 (SSTR2) as a reporter for PET/CT imaging.

Other names

MSLN-targeting R3A CAR T cells