Human IgG subclass cross-species reactivity to mouse and cynomolgus monkey Fcγ receptors

Immunology Letters
Mehabaw G DerebeMark L Chiu

Abstract

In therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. As more candidate antibodies are based on human immunoglobulin (IgG) subclasses, many strategies are pursued to simulate the human system in the test animal. However, translation rate from a successful preclinical trial to an approved drug is extremely low. This may partly be due to differences in interaction of human IgG based candidate molecules to endogenous Fcγ receptors of model animals in comparison to those of human Fcγ receptors. In this study, we compare binding characteristics of human IgG subclasses commonly used in drug development (IgG1, IgG2, IgG4) and their respective Fc silent versions (IgG1σ, IgG2σ, IgG4 PAA) to human, mouse, and cynomolgus monkey Fcγ receptors. To control interactions between Fab and Fc domains, the test IgGs all have the same variable region sequences. We found distinct variations of interaction of human IgG subclasses to model animal Fcγ receptors in comparison to their human counterparts. Particularly, cynomolgus monkey Fcγ receptors showed consistently tighter binding to human IgGs than human Fcγ receptors. M...Continue Reading

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Citations

Jan 24, 2019·Current Protocols in Toxicology·Padma Kumar Narayanan, Nianyu Li
Dec 11, 2019·Antibodies·Mark L ChiuGary L Gilliland
Mar 7, 2019·Frontiers in Immunology·Kashyap R PatelAdam W Barb
Nov 25, 2018·International Journal of Molecular Sciences·Dale E Johnson
Jul 6, 2021·Biotechnology and Bioprocess Engineering : BBE·Seung Hyun Kang, Chang-Han Lee

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