A novel p53R273H-Selective Bispecific T-Cell Engager: from Clinical TCR clone to Computational Optimization and Functional Validation
26 August 2026 at 08:00
Nguyen and colleagues engineered bispecific TCEs targeting p53R273H neoantigens presented by HLA-C*01:02. Machine learning-guided optimization (Boltz-2/EvotProGrad) yielded TCE01Cr3 (Kd = 2.51 nM), a small, high-affinity, specific TCE with mouse serum stability (t1/2 β 40 h), and monotherapy efficacy (> 80% tumor elimination in 3D models) without off-target toxicity or chemotherapy.