Identification of a Guinea Pig Fcγ Receptor that Exhibits Enhanced Binding to Afucosylated Human and Mouse IgG
Changchuin Mao, Richard Near and Wenda Gao*
Antagen Pharmaceuticals, Inc. Boston, MA 02118, USA
- *Corresponding Author:
- Wenda Gao
Antagen Pharmaceuticals, Inc.
650 Albany St., STE 112, Boston
MA 02118, USA
E-mail: [email protected]
Received Date: September 13, 2016; Accepted Date: September 19, 2016; Published Date: September 26, 2016
Citation: Mao C, Near R, Gao W (2016) Identification of a Guinea Pig Fcγ Receptor that Exhibits Enhanced Binding to Afucosylated Human and Mouse IgG. J Infect Dis Med 1:102. DOI: 10.4172/2576-1420.1000102
Copyright: © 2016 Mao C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glyco-engineered recombinant antibodies are currently being developed as the next generation therapeutics to treat human diseases, including cancer, autoimmunity and infection. Antibodies lacking core fucosylation show great increase in affinity for FcγRIIIA, leading to an improved receptor-mediated effector function. While afucosyl human IgG1 exhibits 50-100-fold increase in antibody-mediated cellular cytotoxicity (ADCC), a key immune effector mechanism underlying the anti-cancer effect of some approved therapeutic antibodies, it is not clear whether such glyco-engineered antibodies would find similar use for infectious disease. Due to the species difference, human antibodies may have different binding properties towards corresponding IgG receptors from animals used for modeling infection and intoxication. During the course of studying a recombinant human IgG1 in neutralizing diphtheria toxin (DT) in Guinea pigs (Cavia porcellus), we identified a previously uncharacterized Guinea pig protein H0VDZ8 from UNIPROT database that shows high sequence homologies to human FcγRIIIA and mouse FcγRIV. This Fcγ receptor, which we named as gpFcγRIV, also demonstrates functional similarity although not to the same extent as the human and mouse counterparts, in that it binds to afucosyl human and mouse IgG much stronger than to the wild type antibodies. Thus, Guinea pigs can be used to compare the efficacies of wild type vs. afucosyl anti-DT human IgG1 in toxin removal and animal protection. Molecular and functional characterization of human FcγRIIIA and mouse FcγRIV equivalents in other species could expand the list of preclinical animal models for testing afucosyl human antibodies in treating various human diseases.