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Fc Optimization

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Fc Optimization Platform

MacroGenics has applied its antibody engineering expertise to develop a powerful platform for optimizing monoclonal antibodies. By introducing certain mutations into the Fc domain of an antibody, MacroGenics is able to modulate antibody interaction with effector cells, which activate the body’s immune system.

The Fc domain mediates the antibody’s function by binding to different activating receptors and inhibitory receptors on immune effector cells. The activating receptors lead the cells to internalize or build a response against the target, thus enhancing the immune system’s ability to eliminate a target cell. The inhibitory receptors assist in dampening the immune reaction as to avoid over-activation of the effector cells populations. By engineering Fc regions to bind with optimal levels of affinity to both the activating and inhibitory receptors, MacroGenics has been able to provide more effective immune modulation and improve effector functions, such as cytotoxic potency.

MacroGenics has established a proprietary platform to engineer, screen, identify and test Fc domains with customizable activity. In particular, the company has exclusive access to transgenic mice that express human Fc receptors. These mice can be used for in vivo testing of antibodies that incorporate Fc domain variants, including those antibodies intended for cancer therapy.

To date, MacroGenics has successfully incorporated several of its Fc variants in the company’s lead development candidates. The company has substantial preclinical evidence that these Fc variants have substantially improved the antibody’s therapeutic effects. The company is actively recruiting patients for clinical studies of its Fc-optimized product candidate MGAH22, which targets HER2, and its second Fc-optimized product candidate, MGA271, which targets B7-H3.

Fc Optimization Enhances Antibody-mediated Effector Function