Enhancement of Antibody Functions Through Fc Multiplications

Wang Q, et al., 9(3):393-403, Mabs, 2017

The crystallizable fragment (Fc) domain of an IgG antibody molecule presents an excellent target for protein engineering to develop antibodies with better therapeutic effects. Described herein is the engineering of tandem IgG1 Fc molecules by adding one or two extra copies of Fcs and assessing the effects of Fc multiplication (or tandem Fc) on antibody functions. Furthermore, authors have investigated the functional activities of these newly developed antibodies both in vitro and in vivo. All expressed IgG variants were quantified by using Bio-Layer Interferometry (BLI). A Pall ForteBio Octet QK384 system equipped with Protein A (Pro A) Biosensor probes was used to perform BLI experiments. Authors have observed a significant enhancement of protection provided by the antibodies with 3 Fc tandem repeats in a Klebsiella pneumoniae mouse therapeutic model. The observations of this study reveal a new Fc engineering technology with an unique ability to expand the development of improved antibody therapeutics.

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