title: IgG Fc Fragment as a Scaffold for Development of Targeted Therapeutics.
abstract: Monoclonal antibodies and Fc fusion proteins have been successful therapeutics in the field of cancer and immune disease. As their pharmacological activity is dependent on the Fc fragment governing their effector functions and long in vivo half-life, the extensive engineering of the Fc for altered binding of its natural ligands that enable these properties has delivered molecules optimized for their therapeutic effect. Recently, the IgG1 Fc region itself and its subunits monomeric Fc fragment, CH2 and monomeric CH3 domain, have been engineered into scaffolds with favorable biophysical properties and a high potential for de novo antigen recognition. A dimeric Fc fragment with an antigen binding site has proven suitable for evaluation in animal models and has already entered human trials. Such modified constant domains can easily be incorporated into an antibody or fused with antibody domains of a second specificity. The small size of the Fc and its subunits that enhances their tissue penetration, as well as the unique topology of their binding sites that allows novel modes of contact with the antigen, are attractive features that prompt their development into promising candidate therapeutics.
authors.forename: Gordana W
authors.initials: GW
authors.lastname: Knopp
authors.forename: Gerhard
authors.initials: G
authors.lastname: Stadlmayr
authors.affiliation: University of Natural Resources and Life Sciences, Vienna, Department of Biotechnology, Christian Doppler Laboratory for Innovative Immunotherapeutics, Muthgasse 18, 1190 Vienna, Austria.. Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Ruker
keywords: Directed evolution; Fc fragment; molecular recognition; protein display; protein engineering; rational mutagenesis