贝伐珠单抗生物类似药BAT1706体外生物学活性相似性研究  

In vitro functional similarity assessment of a proposed biosimilar BAT1706 to bevacizumab

作　　者：邓春平 陈航 王英华 梁神娣 曹迪 俞金泉 李胜峰 刘翠华 DENG Chun-ping;CHEN Hang;WANG Ying-hua;LIANG Shen-di;CAO Di;YU Jin-quan;LI Sheng-feng;LIU Cui-hua(Bio-Thera Solutions,Ltd.,Guangzhou 510530,China)

机构地区：[1]百奥泰生物制药股份有限公司,广东广州510530

出　　处：《药学学报》2021年第7期1927-1935,共9页Acta Pharmaceutica Sinica

基　　金：国家“重大新药创制”科技重大专项资助项目(2013ZX09401001);广东省引进创新创业团队资助项目(2013Y116).

摘　　要：生物类似药是在质量、安全性和有效性方面与已获准注册的参照药具有相似性的治疗用生物制品。BAT1706是百奥泰生物制药股份有限公司研发的一款贝伐珠单抗生物类似药,可与血管内皮生长因子A(vascular endothelial growth factor A,VEGF-A)特异性结合,阻断其与内皮细胞表面VEGF受体(VEGF receptor,VEGFR)的结合,阻断配体-受体介导的下游信号通路,抑制内皮血管新生,从而抑制肿瘤生长。采用多种分析技术对BAT1706与原研药Avastin^(■)的体外生物学功能活性进行了全面对比分析,以评价两者的相似性。结果显示,BAT1706与不同形式VEGF-A的结合活性同Avastin^(■)高度相似;两者中和VEGF-A的生物学活性等效,抑制VEGF-A介导的VEGFR-2自磷酸化活性高度相似;此外,BAT1706与不同类型Fcγ受体的亲和力同Avastin^(■)高度相似,且两者均不能诱导肿瘤细胞产生抗体依赖的细胞介导的细胞毒性作用(antibody-dependent cell-mediated cytotoxicity,ADCC)及补体介导的细胞毒性作用(complement-dependent cytotoxicity,CDC)效应。本研究证明了BAT1706与Avastin^(■)在体外生物学功能活性方面的相似性。Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality,safety,and efficacy.BAT1706 is being developed by Bio-Thera Solutions,Ltd.as a proposed biosimilar candidate to bevacizumab reference product(Avastin^(■)).Bevacizumab acts by specifically binding to vascular endothelial growth factor A(VEGF-A),and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells,then blocking the downstream signaling pathway mediated by ligand-receptor,and inhibiting endothelial angiogenesis,thus inhibiting tumor growth.Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin^(■).BAT1706 and Avastin^(■) showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity,as well as inhibitory activity of VEGF receptor(VEGFR)-2 tyrosine kinase autophosphorylation.Both products exhibited similar binding of the Fcγreceptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity(ADCC)and complementdependent cytotoxicity(CDC).Overall,the results demonstrate that BAT1706 and Avastin^(■) are highly similar in terms of in vitro functional activities.

关 键 词：血管内皮生长因子 贝伐珠单抗 生物类似药 相似性 生物学活性 

分 类 号：R917[医药卫生—药物分析学]