Nature communications · 2024
An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Xu Jin-Gen, Chen Shi, He Yang, Zhu Xi, Wang Yanting, Ye Zhifeng, Zhou Jin Chuan, Wu Xuanhui, Zhang Lei, Ren Xiaochen, Jia Huifeng, Yu Haijia, Wei Xiaoyue, Feng Yujie, Chen Xiaofang, Cui Xiaopei, Pan Xianfei, Wang Shaojie, Xia Simin, Shang Hongjie, Pu Yueqing, Xu Wei, Li Haidong, Chen Qian, Chen Zeyu, Wang Manfu, Yan Xiaodong, Shi Hui, Li Mingwei, Xia Yisui, Bellelli Roberto, Dong Shunli, He Jun, Huang Jun, Cai Chen-Leng, Zhu Xiangyang, Zhan Yifan, Wan Li
Аннотация
CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045. HB0045 is a 1:1 mixture of two humanized monoclonal IgG1 antibodies (mAbs), HB0038 and HB0039. The cocktail not only harnesses the advantages of its parental mAbs in enzyme inhibition but also shows a significantly greater capability of promoting T cell proliferation in vitro. Structural analyses show that HB0045 effectively locks the CD73 dimer in a "partially open" non-active conformation through a double lock mechanism. In various animal models of syngeneic and xenograft tumors, HB0045 inhibits tumor growth more potently than the single mAbs. Collectively, our findings provide functional and structural insights into the mechanism of a CD73-targeting antibody cocktail.