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Antibodies 2013, 2(2), 353-370; doi:10.3390/antib2020353

The Development of Bispecific Hexavalent Antibodies as a Novel Class of DOCK-AND-LOCKTM (DNLTM) Complexes

Immunomedics, Inc., Morris Plains, NJ 07950, USA
IBC Pharmaceutical, Inc., Morris Plains, NJ 07950, USA
Garden State Cancer Center, Center of Immunology and Molecular Medicine, Morris Plains, NJ 07950, USA
Authors to whom correspondence should be addressed.
Received: 1 March 2013 / Revised: 9 May 2013 / Accepted: 13 May 2013 / Published: 23 May 2013
(This article belongs to the Special Issue Bispecific Antibodies for Dual Targeting Strategies)
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The DOCK-AND-LOCKTM (DNLTM) method provides a modular approach to develop multivalent, multifunctional complexes of defined structures, of which bispecific hexavalent antibodies (bsHexAbs) are prominent examples with potential applications in targeted therapy for malignant, autoimmune, and infectious diseases. Currently, bsHexAbs are constructed by derivatizing a divalent IgG, at the carboxyl termini of either the heavy chain (the CH3-format) or the light chain (the Ck-format), to contain two stabilized dimers of Fab having a different specificity from the IgG. In this review, we briefly outline the features of the DNLTM method and describe key aspects of bsHexAbs examined with diverse preclinical studies, which include binding affinity to target cells, induction of signaling pathways, effector functions, serum stability, pharmacokinetics, and antitumor activity in human tumor xenograft models. Our findings favor the selection of the CK- over the CH3-format for further exploration of bsHexAbs in clinical trials. View Full-Text
Keywords: DNLTM; bispecific; hexavalent; conjugation; site-specific; antibodies; cancer DNLTM; bispecific; hexavalent; conjugation; site-specific; antibodies; cancer

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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Chang, C.-H.; Rossi, E.A.; Wang, Y.; Cardillo, T.M.; Goldenberg, D.M. The Development of Bispecific Hexavalent Antibodies as a Novel Class of DOCK-AND-LOCKTM (DNLTM) Complexes. Antibodies 2013, 2, 353-370.

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