@inproceedings{d536d0595c6546f59f2497d987fd7d29,
title = "Engineering high-affinity ociperlimab mutants through structure-based antibody optimization",
abstract = "TIGIT acts as a pivotal inhibitory receptor mediating T-cell dysfunction and immune evasion. Using structure-guided saturation mutagenesis of Ociperlimab, we identified several variants, most notably the pentamutant Ociperlimab MP5 and the single-point mutant Ociperlimab SP16, which exhibited significantly improved binding free energies. Beyond affinity enhancement, these mutants demonstrated optimized developability profiles, including reduced aggregation propensity and a marked increase in heavy-chain humanization. Mechanistic analyses revealed that these optimized variants strengthen key interface interactions, enhancing T-cell activation and effector functions. In vitro and in vivo studies demonstrated improved immune responses, including increased T-cell proliferation and functional cytokine secretion. These results provide a mechanistic framework for rational antibody optimization, offering a pathway to more effective TIGIT-targeted immunotherapies.",
keywords = "Immune checkpoint inhibitors, Mechanistic study, Ociperlimab mutant, T cell function, TIGIT",
author = "Ruichen Liu and Yi Zhao and Jianhua Liang and Qi Zhang and Mingjia Yu",
note = "Publisher Copyright: {\textcopyright} COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only.; 2025 International Conference on Imaging Processing for Medical-Oriented Recognition, IPOR 2025 ; Conference date: 27-11-2025 Through 29-11-2025",
year = "2026",
month = mar,
day = "19",
doi = "10.1117/12.3106798",
language = "English",
series = "Proceedings of SPIE - The International Society for Optical Engineering",
publisher = "SPIE",
editor = "Yee, \{Por Lip\} and Gadekallu, \{Thippa Reddy\}",
booktitle = "International Conference on Imaging Processing for Medical-Oriented Recognition, IPOR 2025",
address = "United States",
}