Humanization and characterization of the anti-HLA-DR antibody 1D10

被引:47
作者
Kostelny, SA
Link, BK
Tso, JY
Vasquez, M
Jorgensen, BH
Wang, H
Hall, WC
Weiner, GJ
机构
[1] Univ Iowa, Holden Comprehens Canc Res, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
[3] Prot Design Labs Inc, Fremont, CA USA
[4] Pathol Associates Int, Frederick, MD USA
关键词
lymphoma; monoclonal antibody; immunotherapy; MHC class II; HLA-DR;
D O I
10.1002/ijc.1366
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
ID10 is a previously described antibody that binds to cells from a majority of B-cell malignancies, The current studies were designed to further evaluate the antigen specificity of ID10 and its potential as an immunotherapeutic agent, Studies with transfectants and immunoprecipitation demonstrated that ID10 recognizes some, but not all, of the human HLA-DR beta chains, Both normal and malignant B cells can express the ID10 antigen. A humanized version of ID10 was produced using CDR grafting. The resulting antibody has an affinity that is similar to that of the parental murine antibody. In addition, the humanized antibody is capable of inducing complement-mediated cytotoxicity, antibody-dependent cell cytotoxicity, and direct apoptosis of I D IO-expressing B cells, Based on these in vitro anti-tumor activities, we conclude humanized ID10 deserves further evaluation as an immunotherapeutic agent, (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:556 / 565
页数:10
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