Engineered antibody variable and constant domains as therapeutic candidates.

Monoclonal antibodies have been successfully used for the therapy of various diseases. However, because of their large size (∼150 kD), many limitations have also been found during their development and manufacture. The use of antibody fragments with smaller sizes is one of the strategies to overcome these limitations. Antibody heavy chain variable domains (12∼15 kD) have already been widely used for the development of variable domain-based engineered antibody domains (termed V-based eAds) targeting different antigens. Recently, antibody second heavy chain constant domains (∼12 kD) were proposed as novel scaffolds for library construction and selection of specific binders termed constant domain-based eAds (C-based eAds) as novel candidate therapeutics, which might also confer additional crystallizable fragment functions. Both V- and C-based eAds are promising therapeutic candidates. This review summarizes progress in the development of eAds, and discusses the related patents and their potential applications.