title: Generation of Bispecific Antibodies by Fc Heterodimerization and their Application.
abstract: 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 application.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Tianshu
authors.initials: T
authors.lastname: Xu
authors.forename: Qifei
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, Beijing, China.. China.
authors.forename: Lishan
authors.initials: L
authors.lastname: Kang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
keywords: Bispecific antibody; Fc heterodimerization; Knobs-into-holes; quadroma; strand-exchange engineered domain