Functional Antagonism of Human CD40 Achieved by Targeting a Unique Species-Specific Epitope
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- 作者：Aaron P. Yamniuk1 ; aaron.yamniuk@bms.com" class="auth_mail" title="E-mail the corresponding author ; Anish Suri2 ; 4 ; Stanley R. Krystek1 ; James Tamura1 ; 5 ; Vidhyashankar Ramamurthy1 ; 6 ; Robert Kuhn2 ; 7 ; Karen Carroll2 ; Catherine Fleener2 ; 8 ; Rolf Ryseck1 ; Lin Cheng1 ; Yongmi An1 ; Philip Drew3 ; 9 ; Steven Grant3 ; 9 ; Suzanne J. Suchard2 ; Steven G. Nadler2 ; James W. Bryson1 ; Steven Sheriff1 ; steven.sheriff@bms.com" class="auth_mail" title="E-mail the corresponding author
- 关键词：APCs ; antigen-presenting cells ; mAbs ; monoclonal antibodies ; dAbs ; domain antibodies ; NHPs ; nonhuman primates ; hCD40 ; human CD40 ; DC ; dendritic cell ; CDR ; complementarity-determining region ; SPR ; surface plasmon resonance ; NHS ; N-hydroxysuccinimide ; SEC ; size exclusion chromatography ; PBST ; PBS containing Tween 20 ; RU ; resonance units ; IZ ; isoleucine zipper ; IZ-hCD40L ; trimeric IZ human-CD40L ; iDCs ; immature DCs ; RB ; round bottom
- 刊名：Journal of Molecular Biology
- 出版年：2016
- 出版时间：17 July 2016
- 年：2016
- 卷：428
- 期：14
- 页码：2860-2879
- 全文大小：2069 K
文摘
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Can agonist and antagonist activities be separated for CD40 therapeutic agents?
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dAbs identified with unique human-specific antagonist epitope.
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X-ray crystal structures show molecular details of dAb and antibody epitopes.
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Cynomolgus-specific surrogate dAb molecules generated, also potent antagonist
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dAbs targeted to unique epitope are functional antagonists as bivalent Fc-fusion.