检索结果-南通市图书馆

BGB-A445,a novel non-ligand-blocking agonistic anti-ox40 antibody,exhibits superior immune activation and antitumor effects in preclinical models

引用

Frontiers of Medicine 2023年第6期17卷 1170-1185页

作者： Beibei Jiang Tong Zhang Minjuan Deng Wei Jin Yuan Hong Xiaotong Chen Xin Chen Jing Wang Hongjia Hou Yajuan Gao Wenfeng Gong Xing Wang Haiying li Xiaosui Zhou Yingcai Feng Bo Zhang Bin Jiang Xueping lu lijie Zhang Yang li Weiwei Song Hanzi Sun Zuobai Wang Xiaomin Song Zhirong Shen Xuesong liu Kang li lai Wang Ye liu Department of Biology BeiGene(Beijing)Co.Ltd.Beijing 102206China Department of Discovery Biomarkers BeiGene(Beijing)Co.Ltd.Beijing 102206China Department of Clinic Development BeiGene(Beijing)Co.Ltd.Beijing 102206China Department of Biologics BeiGene(Beijing)Co.Ltd.Beijing 102206China

t ox40 is a costimulatory receptor that is expressed primarily on activated CD4+,CD8+,and regulatory T cells.The ligation of ox40 to its sole ligand ox40l potentiates T cell expansion,differentiation,and activation and also promotes dendritic cells to mature to enhance their cytokine production.Therefore,the use of agonistic anti-ox40 antibodies for cancer immunotherapy has gained great interest.However,most of the agonistic anti-ox40 antibodies in the clinic are ox40l-competitive and show limited efficacy.Here,we discovered that BGB-A445,a non-ligand-competitive agonistic anti-ox40 antibody currently under clinical investigation,induced optimal T cell activation without impairing dendritic cell function.In addition,BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity.In the MC38 syngeneic model established in humanized ox40 knock-in mice,BGB-A445 demonstrated robust and dose-dependent antitumor efficacy,whereas the ligand-competitive anti-ox40 antibody showed antitumor efficacy characterized by a hook effect.Furthermore,BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody.Taken together,our findings show that BGB-A445,which does not block ox40-ox40l interaction in contrast to clinical-stage anti-ox40 antibodies,shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

关键词： BGB-A445 ox40 agonistic antibody ox40l noncompetitive

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：