Article
Overcoming T cell tolerance to tumor self-antigens through catch-bond engineering.
Science (New York, N.Y.) - 19 Mar 2026
Chen Xiaojing, Mao Zhiyuan, Kolawole E Motunrayo, Persechino Margherita, Jude Kevin M, Ogishi Masato, Mo Kelvin C, McLaughlin Jami, Cheng Donghui, Xiang Xinyu, Yang Xinbo, Gee Caitlin, Liu Shiqin, Yang Aerin, Obenaus Matthias, Wang Nan, Noguchi Miyako, Stoyanova Tanya, Lee John K, Good Zinaida, Latorraca Naomi R, Evavold Brian D, Witte Owen N, Garcia K Christopher
Abstract excerpt
T cells are often weakly responsive to tumor self-antigens because of central tolerance, constraining their ability to eliminate tumors. We exploited mechanical force to engineer a weakly reactive T cell receptor (TCR) specific for a nonmutated tumor-associated antigen (TAA), prostatic acid phosphatase (PAP). We identified a catch-bonding "hotspot" whose mutation enhanced T cell activity by increasing TCR-pMHC...
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