Engineering therapeutic bispecific antibodies using CrossMab technology

Publication date: Available online 16 November 2018Source: MethodsAuthor(s): Christian Klein, Wolfgang Schaefer, Joerg T Regula, Charles Dumontet, Ulrich Brinkmann, Marina Bacac, Pablo UmañaAbstractBispecific antibodies have recently gained major interest as they allow novel mechanisms-of-action and/or therapeutic applications that cannot be achieved using conventional IgG-based antibodies. A major issue in engineering IgG-based bispecific antibodies has been to enable the correct association of heavy and light chains resulting in correct assembly of the desired bispecific antibody in sufficient yield. Various approaches have been described during recent years to tackle this challenge. We have developed the so-called CrossMab technology that enforces correct light chain association based on the domain crossover of immunoglobulin domains in the Fab region of the bispecific antibody. This versatile technology allows the generation of different bispecific antibody formats including asymmetric heterodimeric monovalent 1+1 bispecific antibodies and asymmetric heterodimeric bispecific antibodies with 2+1 valency in combination with approaches enabling Fc-hetermodimerization like knob-into-hole technology as well as the generation of tetravalent symmetric bispecific antibodies with 2+2 valency, also known as Tandem-Fab based IgG antibodies, using processes suitable for the large scale production of therapeutic bispecific antibodies. Notably, as of now, at least eight different bisp...
Source: Methods - Category: Molecular Biology Source Type: research