Nonclinical immunogenicity risk assessment for knobs-into-holes bispecific IgG1 antibodies [PDF]
mAbsBispecific antibodies, including bispecific IgG, are emerging as an important new class of antibody therapeutics. As a result, we, as well as others, have developed engineering strategies designed to facilitate the efficient production of bispecific IgG ...
Wen-Ting K. Tsai +15 more
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Production of bispecific antibodies in “knobs-into-holes” using a cell-free expression system [PDF]
MAbs, 2015 Bispecific antibodies have emerged in recent years as a promising field of research for therapies in oncology, inflammable diseases, and infectious diseases. Their capability of dual target recognition allows for novel therapeutic hypothesis to be tested, where traditional mono-specific antibodies would lack the needed mode of target engagement.
Gang Yin +2 more
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Knobs-into-holes antibody production in mammalian cell lines reveals that asymmetric afucosylation is sufficient for full antibody-dependent cellular cytotoxicity [PDF]
MAbs, 2013 Knobs-into-holes is a well-validated heterodimerization technology for the third constant domain of an antibody. This technology has been used to produce a monovalent IgG for clinical development (onartuzumab) and multiple bispecific antibodies. The most advanced uses of this approach, however, have been limited to E.
Justin Scheer +2 more
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Heavy and light chain pairing of bivalent quadroma and knobs-into-holes antibodies analyzed by UHR-ESI-QTOF mass spectrometry [PDF]
MAbs, 2016 The quadroma antibody represents the first attempt to produce a bispecific heterodimeric IgG antibody by somatic fusion of 2 hybridoma cells each expressing monoclonal antibodies with distinctive specificities. However, because of random heavy and light chain pairing, the desired functional bispecific antibody represents only a small fraction of the ...
Christian Klein +2 more
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Rapsyn's knobs and holes: eight tetratrico peptide repeats [PDF]
Biochemical Journal, 1996 Ponting CC, Phillips C.
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Effect of allotypic variation of human IgG1 on the thermal stability of disulfide-linked knobs-into-holes mutants of the Fc for stable bispecific antibody design. [PDF]
Antib Ther, 2019 AbstractBackgroundDisulfide-linked knobs-into-holes (dKiH) mutation is a well-validated antibody engineering technique to force heterodimer formation of different Fcs for efficient production of bispecific antibodies. An artificial disulfide bond is created between mutated cysteine residues in CH3 domain of human IgG1 Fc whose positions are 354 of the “
Akiba H, Satoh R, Nagata S, Tsumoto K.
europepmc +4 more sources
Construction of bispecific antibodies by specific pairing between the heavy chain and the light chain using removable SpyCatcher/SnoopCatcher units [PDF]
Journal of Biological EngineeringDuring the production of bispecific antibodies (bsAbs), nonspecific pairing results in low yields of target bsAb molecules, an issue known as the “mispairing problem.” Several antibody engineering techniques have been developed to overcome mispairing ...
Jyunna Yoshida +7 more
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Physicochemical and biological characterization of a bispecific antibody in a CrossMab/KIH format that targets EGFR and VEGF-A [PDF]
Frontiers in ImmunologyIntroductionBispecific antibodies (BsAbs) are a class of antibody therapeutics engineered in various molecular formats to bind two distinct antigens and potentially mediate multiple biological effects.
Safiat Ayinde +3 more
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Aglycosylated knob and hole Fc homodimers are anti-parallel [PDF]
Acta Crystallographica Section A Foundations and Advances, 2014 Bispecific antibody and antibody-like molecules are of wide interest as potential therapeutics that can recognize two distinct targets. Among the variety of ways such molecules have been engineered is by creating ""knob"" and ""hole"" heterodimerization sites in the CH3 domains of two antibody heavy chains.
Mark Ultsch +7 more
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Bispecific antibodies with Fab-arms featuring exchanged antigen-binding constant domains
Biochemistry and Biophysics Reports, 2021 Monoclonal antibodies can acquire the property of engagement of a second antigen via fusion methods or modification of their CDR loops, but also by modification of their constant domains, such as in the mAb2 format where a set of mutated amino acid ...
Filippo Benedetti +5 more
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