title: Engineered Fc based antibody domains and fragments as novel scaffolds.
abstract: Therapeutic monoclonal antibodies (mAbs) have been successful for the therapy of a number of diseases mostly cancer and immune disorders. However, the vast majority of mAbs approved for clinical use are full size, typically in IgG1 format. These mAbs may exhibit relatively poor tissue penetration and restricted epitope access due to their large size. A promising solution to this fundamental limitation is the engineering of smaller scaffolds based on the IgG1 Fc region. These scaffolds can be used for the generation of libraries of mutants from which high-affinity binders can be selected. Comprised of the CH2 and CH3 domains, the Fc region is important not only for the antibody effector function but also for its long half-life. This review focuses on engineered Fc based antibody fragments and domains including native (dimeric) Fc and monomeric Fc as well as CH2 and monomeric CH3, and their use as novel scaffolds and binders. The Fc based binders are promising candidate therapeutics with optimized half-life, enhanced tissue penetration and access to sterically restricted binding sites resulting in an increased therapeutic efficacy. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody.
authors.affiliation: Protein Interactions Group, Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health (NIH), Frederick, MD 21702, USA. Electronic address: tianlei.ying@nih.gov.
authors.forename: Tianlei
authors.initials: T
authors.lastname: Ying
authors.affiliation: Antibody Engineering Group, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gong
authors.affiliation: Protein Interactions Group, Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health (NIH), Frederick, MD 21702, USA.
authors.forename: Tina W
authors.initials: TW
authors.lastname: Ju
authors.affiliation: Protein Interactions Group, Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health (NIH), Frederick, MD 21702, USA; Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Ponraj
authors.initials: P
authors.lastname: Prabakaran
authors.affiliation: Protein Interactions Group, Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health (NIH), Frederick, MD 21702, USA.
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
keywords: Antibody engineering; CH2 domain; CH3 domain; Domain antibody; Monoclonal antibody; Monomeric Fc