Cell-type specific potent Wnt signaling blockade by bispecific antibody.
Cell-type specific potent Wnt signaling blockade by bispecific antibody.
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DOI：
10.1038/s41598-017-17539-z
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发表时间：
2018-01-15
影响因子：
4.6
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Lee NK;Zhang Y;Su Y;Bidlingmaier S;Sherbenou DW;Ha KD;Liu B
Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity. We found that the bispecific antibody inhibits Wnt-induced reporter activities with over one hundred-fold enhancement in potency, and in a cell type-selective manner. Potency enhancement is dependent on the expression level of the guide antigen on the target cell surface and the apparent affinity of the anti-guide antibody. Both internalizing and non-internalizing guide antigens can be used, with internalizing bispecific antibody being able to block signaling by all ligands binding to the target receptor due to its removal from the cell surface. It is thus feasible to develop bispecific-based therapeutic strategies that potently and selectively inhibit signaling pathways in a cell type-selective manner, creating opportunity for therapeutic targeting.
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DOI：
10.1083/jcb.201107021
发表时间：
2011-09-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Berndt JD;Aoyagi A;Yang P;Anastas JN;Tang L;Moon RT
通讯作者：
Moon RT
影响因子：
4.7
作者：
Conrad, Fraser;Zhu, Xiaodong;Zhang, Xin;Chalkley, Robert J.;Burlingame, Alma L.;Marks, James D.;Liu, Bin
通讯作者：
Liu, Bin
影响因子：
3.3
作者：
Kim, Kyung-Ah;Wagle, Marie;Abo, Arie
通讯作者：
Abo, Arie
影响因子：
7.5
作者：
Holland, Jane D.;Klaus, Alexandra;Birchmeier, Walter
通讯作者：
Birchmeier, Walter
影响因子：
4.8
作者：
Bourhis, Eric;Tam, Christine;Hannoush, Rami N.
通讯作者：
Hannoush, Rami N.