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.
Xu Y +10 more
europepmc +5 more sources
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
doaj +4 more sources
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.
Shatz W +8 more
europepmc +5 more sources
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 +6 more sources
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 ...
Schaefer W +6 more
europepmc +5 more sources
Excellent removal of knob-into-hole bispecific antibody byproducts and impurities in a single capture chromatography [PDF]
Bioresources and Bioprocessing, 2022 AbstractBispecific antibodies (bsAbs) are therapeutically promising due to their ability to bind to two different antigens. However, the bsAb byproducts and impurities, including mispaired homodimers, half-antibodies, light chain mispairings, antibody fragments and high levels of high molecular weight (HMW) species, all pose unique challenges to their ...
Serene W. Chen +4 more
+8 more sources
Effective flow-through polishing strategies for knob-into-hole bispecific antibodies [PDF]
Bioresources and Bioprocessing, 2022 AbstractBispecific antibodies (bsAbs), though possessing great therapeutic potential, are extremely challenging to obtain at high purity within a limited number of scalable downstream processing steps. Complementary to Protein A chromatography, polishing strategies play a critical role at removing the remaining high molecular weight (HMW) and low ...
Serene W. Chen +4 more
openalex +4 more sources
Detailed Analytical Characterization of a Bispecific IgG1 CrossMab Antibody of the Knob-into-Hole Format Applying Various Stress Conditions Revealed Pronounced Stability [PDF]
ACS Omega, 2022 In recent years, a variety of new antibody formats have been developed. One of these formats allows the binding of one type of antibody to two different epitopes. This can for example be achieved by introduction of the "knob-into-hole" format and a combined CrossMab approach.
Ingrid Grunert +8 more
openalex +5 more sources
Non-affinity platform for processing knob-into-hole bispecific antibody [PDF]
Bioresources and BioprocessingAbstract Bispecific antibodies hold significant potential as next-generation biotherapeutics owing to their ability to simultaneously bind to two targets. However, the development of bispecific antibodies as biotherapeutics has been hindered by the high levels of byproducts produced, including both high molecular weight and low ...
X. Wang +5 more
+7 more sources
Vector design for enhancing expression level and assembly of knob-into-hole based FabscFv-Fc bispecific antibodies in CHO cells [PDF]
Antibody Therapeutics, 2022 Abstract Background Two-armed FabscFv-Fc is a favoured bispecific antibody (BsAb) format due to its advantages of the conventional IgG structure. Production of FabscFv-Fc requires expression of three polypeptide chains, one light chain (LC), one heavy chain (HC) and a scFv fused to the Fc (scFvFc) at ...
Han Kee Ong +3 more
openalex +3 more sources