Next Generation monoclonal antibody therapies targeting the inhibitory FcR.

Designing and engineering the next generation monoclonal antibody therapies targeting the inhibitory Fc Receptors.

Our Immune Therapies program will create the first truly selective therapeutic mAbs to harness the powerful and normal inhibitory power of our own immune system - to inactivate inflammatory cells.

A new concept in immune therapy is using mAbs to switch off life threatening destructive inflammation. There is a serious unmet need in treatment of inflammatory diseases where the immune system is hyper-activated and lacks control. This includes diseases such as allergy and the auto-inflammatory diseases lupus (SLE), rheumatoid arthritis and related diseases.

Aims:

We are designing and engineering a new class of medicines - “Fc engineered monoclonal antibodies” (mAbs) and use these to co-opt the immune system’s normal inhibitory system to switch off inflammatory white blood cells.

Progress

The immune system initiates powerful destructive inflammatory processes but the system also has checks and balances including the most powerful modulator of inflammatory responses - the inhibitory-type Fc receptor (FcγRIIb). This receptor is a potent “off-switch” of inflammatory white blood cells.

Our discoveries now make it possible for us to develop a completely new class of potent highly selective, therapeutic mAbs that harness the body’s normal inhibitory control mechanism to eliminate inflammation in allergy and related diseases. Our initial discovery showed it was in principle possible to engineer mAbs to have selective anti-inflammatory properties and create a new class of anti-inflammatory medicines.

We have used different scaffolds to create several unique mAbs with powerful inhibitory action in allergic cells in blood. We are working to improve potency and apply this “platform” to other inflammatory disease.

Significance and outcomes – potential for new therapies:

• New therapies for an unmet need in allergies, lupus and autoimmune inflammation.
• To understand the role of the IL-23 receptor system in inflammation.
• A new antibody engineering strategy that can be adapted to generate new medicines for the treatment of other inflammatory diseases, e.g. lupus.

Outcomes

Hogarth PM and Pietersz GA. Fc receptor targeted therapies for the treatment of Inflammation, Cancer and Beyond. Nature Reviews Drug Discovery 11:311-331 2012.