机构：[1]School of Life Sciences and Technology, Tongji University, Shanghai, China.[2]Panorama Research Institute, Sunnyvale, CA, USA.[3]Shanghai Tongji Hospital, Tongji University, Shanghai, China.[4]Tongji University Suzhou Institute, Suzhou, China.[5]Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.四川大学华西医院[6]Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Therapeutic antibodies are effective for tumor immunotherapy and exhibit prominent clinical effects. All approved antibody therapeutics utilize IgG as the molecular format. Antibody-dependent cell-mediated cytotoxicity (ADCC) is a key mechanism for tumor cell killing by antibodies. For IgG antibodies, ADCC depends on FcγR-expressing cells, such as natural killer (NK) cells. However, in patients with a high tumor burden, antibody therapeutics may lose efficacy owing to exhaustion of FcγR-expressing effector cells as well as the inhibitory effects of certain FcγRs on effector cells. To achieve more potent effector functions, we engineered an anti-CD20 antibody to contain both IgG Fc and IgA Fc domains. These engineered antibodies interacted with both IgG and IgA Fc receptors (FcγR and FcαR) and recruited a broader range of effector cells, including monocytes, macrophages, neutrophils, and NK cells, thereby enhancing antibody-dependent cellular phagocytosis. Using transgenic mice expressing the FcαRI (CD89) in macrophages, we demonstrated that recombinant antibodies bearing the chimeric IgG and IgA Fc exhibited potent in vivo antitumor activity. Additionally, in a short-term peritoneal model using CD20-transfected LLC target cells, the in vivo cytotoxic activity of hybrid recombinant antibodies was mediated by macrophages with significant reduction in the absence of FcαRI. Our findings supported targeting of FcαRI on monocytes and macrophages for improved tumor immunotherapy.
基金：
This study was supported by grants from the National Natural Science Foundation of China (NSFC31470896, and NSFC81402399), National Basic Research Program of China (973 Program) 2015CB553706, and Suzhou Applicational Basic Project, China (SYG201509).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区肿瘤学3 区细胞生物学
最新[2023]版：
无
第一作者：
第一作者机构：[1]School of Life Sciences and Technology, Tongji University, Shanghai, China.
共同第一作者：
通讯作者：
通讯机构：[1]School of Life Sciences and Technology, Tongji University, Shanghai, China.[3]Shanghai Tongji Hospital, Tongji University, Shanghai, China.[4]Tongji University Suzhou Institute, Suzhou, China.[5]Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.[6]Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
推荐引用方式(GB/T 7714)：
Li Bingyu,Xu Lijun,Tao Fei,et al.Simultaneous exposure to FcγR and FcαR on monocytes and macrophages enhances antitumor activity in vivo.[J].Oncotarget.2017,8(24):39356-39366.doi:10.18632/oncotarget.17000.
APA：
Li Bingyu,Xu Lijun,Tao Fei,Xie Kun,Wu Zhiqiang...&Fang Jianmin.(2017).Simultaneous exposure to FcγR and FcαR on monocytes and macrophages enhances antitumor activity in vivo..Oncotarget,8,(24)
MLA：
Li Bingyu,et al."Simultaneous exposure to FcγR and FcαR on monocytes and macrophages enhances antitumor activity in vivo.".Oncotarget 8..24(2017):39356-39366
