Generation of Bispecific Antibodies by Fc Heterodimerization and their Application
Bispecific antibodies with binding specificities for two different antigens have prompted a lot
of interest into their development and application. Currently, more than ten bispecific antibodies have
been clinically validated for the treatment of various diseases, including cancers and inflammatory diseases.
Intensive studies in antibody engineering drive the generation of different bispecific antibody
formats that differ in size and shape. However, the most prominent formats, such as IgG-single-chain
(sc) Fv or dual-variable domain (DVD) IgG, deviating from the natural IgG structure, may lead to
manufacturing difficulties or increase the potential risk of immunogenicity. Thus, the recent efforts
focus on the development of bispecific antibodies by Fc heterodimerization that maintain the native
structure of the antibody IgG molecule. This review summarizes the various techniques and methods to
generate bispecific antibody molecules with Fc heterodimerization, and discusses perspectives of their
Keywords: Bispecific antibody, Fc heterodimerization, quadroma, Knobs-into-holes, strand-exchange engineered domain.
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