Article
CD28 Costimulatory Domain-Targeted Mutations Enhance Chimeric Antigen Receptor T-cell Function.
Cancer immunology research - 1 Jan 2021
Boucher Justin C, Li Gongbo, Kotani Hiroshi, Cabral Maria L, Morrissey Dylan, Lee Sae Bom, Spitler Kristen, Beatty Nolan J, Cervantes Estelle V, Shrestha Bishwas, Yu Bin, Kazi Aslamuzzaman, Wang Xuefeng, Sebti Said M, Davila Marco L
Abstract excerpt
An obstacle to the development of chimeric antigen receptor (CAR) T cells is the limited understanding of CAR T-cell biology and the mechanisms behind their antitumor activity. We and others have shown that CARs with a CD28 costimulatory domain drive high T-cell activation, which leads to exhaustion and shortened persistence. This work led us to hypothesize that by incorporating null mutations of CD28 subdomains...
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