Characterization of a humanized anti-CD20 antibody with potent antitumor activity against B-cell lymphoma

被引:10
作者
Wu, Lan [1 ,2 ,3 ]
Wang, Chong [4 ,5 ,6 ,7 ]
Zhang, Dapeng [1 ,2 ,3 ]
Zhang, Xunming [1 ,2 ,3 ]
Qian, Weizhu [1 ,2 ,3 ,4 ,5 ]
Zhao, Lei [1 ,2 ,3 ]
Wang, Hao [1 ,2 ,3 ,4 ,5 ]
Li, Bohua [1 ,2 ,3 ,4 ,5 ]
Guo, Yajun [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
机构
[1] Second Mil Med Univ, Int Joint Canc Inst, Shanghai 200433, Peoples R China
[2] Second Mil Med Univ, Gen Hosp Canc Ctr 301, Shanghai 200433, Peoples R China
[3] Peoples Liberat Army Gen Hosp, Beijing 100853, Peoples R China
[4] Natl Engn Res Ctr Antibody Med, Shanghai 201203, Peoples R China
[5] Shanghai Key Lab Cell Engn & Antibody, Shanghai 201203, Peoples R China
[6] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China
[7] Shanghai Jiao Tong Univ, Sch Pharm, Ctr Antibody Med, Minist Educ, Shanghai 200025, Peoples R China
基金
中国国家自然科学基金;
关键词
CD20; Humanized antibody; Complement-dependent cytotoxicity; B-cell lymphoma; NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODIES; RITUXIMAB TREATMENT; IN-VIVO; MECHANISMS; LYMPHOCYTES; FRAMEWORK; RESIDUES; THERAPY; CD20;
D O I
10.1016/j.canlet.2009.12.004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Despite the effectiveness of the anti-CD20 chimeric antibody (mAb), rituximab, in treating B-cell lymphomas, its efficacy remains variable and often modest. In this study, a humanized anti-CD20 antibody, hu8E4, was generated by complementary-determining region grafting method Hu8E4 was as effective as rituximab in mediating antibody-dependent cellular cytotoxicity and inducing apoptosis in B-lymphoma cells, but it exhibited much more potent complement-dependent cytotoxicity than rituximab Immunotherapeutic studies showed that hu8E4 was significantly more effective than rituximab in prolonging the survival of severe combined immunodeficient mice bearing human B-cell lymphomas, suggesting that It might be a promising therapeutic agent for B-cell lymphomas. (C) 2009 Elsevier Ireland Ltd. All rights reserved
引用
收藏
页码:208 / 214
页数:7
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