Fc Engineering
The Fc is a programmable effector module
Antigen binding determines where an antibody goes. The Fc region helps determine what happens after it arrives.
Wild-type IgG simultaneously engages multiple immune pathways. This makes it difficult to distinguish which effector mechanism drives a therapeutic response and prevents each pathway from being optimized independently.
We engineer Fc domains that separate these functions.
IgG: Structure and functions
IgG: Effector functions
IgG: Subclasses
a Depends on allotype.
Separating complement from Fc receptor activity
We developed IgG1 Fc variants that retain C1q binding while eliminating effector Fcγ receptor engagement. These molecules allowed complement-mediated antibody activity to be examined independently of cellular Fc receptor function.
Nature Immunology, 2017
Dissecting Fcγ receptor function
Using receptor-selective Fc engineering, we showed that FcγRIIIa engagement alone can support antibody-dependent cellular phagocytosis by GM-CSF-differentiated macrophages.
Frontiers in Immunology, 2019
Engineering antibody pharmacokinetics
We redesigned the FcRn interface to create pH-dependent Fc behavior, promoting recycling under acidic conditions and release at physiological pH. This strategy substantially prolonged antibody circulation.
Nature Communications, 2019
From fixed constant region to designed function
Our Fc variants provide a modular starting point for therapeutic antibodies requiring different combinations of cytotoxicity, receptor silence, complement activity, or prolonged exposure.