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Pubmed ID :29476755
Publication Date : //

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


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. Moreover, the presumably Fc silent human IgG4 PAA framework bound to cynomolgus monkey FcγRI with nanomolar affinity while only very weak binding was observed for the human FcγRI. Our results highlighted the need for a thorough in vitro affinity characterization of candidate IgGs against model animal Fcγ receptors and careful design of preclinical studies.

Authors : Derebe Mehabaw G , Nanjunda Rupesh K , Gilliland Gary L , Lacy Eilyn R , Chiu Mark L ,

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MC34-171 Monkey (Cynomolgus) cDNA Normal Tissue: Skeletal Muscle Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-234 Monkey (Cynomolgus) cDNA Normal Tissue: Spinal Cord Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-226 Monkey (Cynomolgus) cDNA Normal Tissue: Small Intestine Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
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MC34-152 Monkey (Cynomolgus) cDNA Normal Tissue: Lung Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-188 Monkey (Cynomolgus) cDNA Normal Tissue: Pancreas Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-267 Monkey (Cynomolgus) cDNA Normal Tissue: Tongue Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-201 Monkey (Cynomolgus) cDNA Normal Tissue: Prostate Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-206 Monkey (Cynomolgus) cDNA Normal Tissue: Rectum Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-218 Monkey (Cynomolgus) cDNA Normal Tissue: Skin Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-274 Monkey (Cynomolgus) cDNA Normal Tissue: Uterus Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
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MC34-035 Monkey (Cynomolgus) cDNA Normal Tissue: Brain Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-248 Monkey (Cynomolgus) cDNA Normal Tissue: Stomach Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-149 Monkey (Cynomolgus) cDNA Normal Tissue: Liver Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-142 Monkey (Cynomolgus) cDNA Normal Tissue: Kidney Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
MC34-122 Monkey (Cynomolgus) cDNA Normal Tissue: Heart Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
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MC34-010 Monkey (Cynomolgus) cDNA Normal Tissue: Bladder Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA
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MC34-086 Monkey (Cynomolgus) cDNA Normal Tissue: Breast Species Reactivity: Monkey (Cynomolgus) 10 rxn Product tipe: cDNA


 

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