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Received β€” 10 September 2026 ⏭ Molecular Therapy Oncology

A novel p53R273H-Selective Bispecific T-Cell Engager: from Clinical TCR clone to Computational Optimization and Functional Validation

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‰ˆ 40 h), and monotherapy efficacy (> 80% tumor elimination in 3D models) without off-target toxicity or chemotherapy.
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