Monoclonal antibodies and natural antibodies use the same mechanism to induce the FcR dependent powerful killing and inflammatory responses. Both types of antibodies must be in close proximity and cluster the FcR of the killer cells and inflammatory white blood cells.
Predicting which antibodies– whether monoclonal or naturally induced by vaccine or infection – will induce potent killing or inflammatory responses requires the use of complex, expensive and specially designed assays and methods.
We are designing cheap, simple and rapid cell free assays using specially designed human Fc receptor proteins are applied to evaluate the quality of antibody responses and to predict their potency.
This project applies the same methodology across a spectrum of applications in cancer; infection and autoimmunity
Our test is cheap, simple and straightforward.
There are four priority applications.
Imaging monoclonal antibody function in the body. Using the engineered Fc receptors we can visualise “functional” therapeutic monoclonal antibodies on cancer cells in the body for the first time. We believe this approach will help inform choice and management of monoclonal antibody therapeutics in patients with a view to “personalising” therapies.
Predicting the quality of natural antibody responses and infection or more importantly in vaccine induced responses. The immune system is designed to produce antibodies to infectious agents. However only a fraction of these are potent inducers of killing anti-inflammatory functions of the white blood cells. The engineered Fc receptor proteins allow us to simply and rapidly evaluate the “quality” of a response following vaccination.
In certain types of auto inflammatory diseases where aberrant naturally produced antibodies cause life-threatening tissue destruction rapid detection of antibodies that induce the destruction can be critically important in the clinical management. Heparin Induced Thrombocytopenia serious life-threatening antibody -induced condition caused by certain antibodies. We can accurately, rapidly, cheaply and simply identify these antibodies in patients. This is a critical advance in the management of this condition in hospitals and allows rapid intervention to prevent death.
In industry a great deal of effort is made to identify “optimal” monoclonal antibodies that have all the desirable characteristics of a potent therapeutic i.e. able to induce NK cell killing, macrophage phagocytosis, inflammatory mediator release. However there is no simple method to rapidly screen potential therapeutic monoclonal antibodies. Our simple specially engineered Fc receptor probes are scalable and potentially allow the rapid high throughput analysis of thousands of candidate therapeutic mAbs.
Significance and outcomes – potential for new therapies:
• Industry Simple function-based test for vaccine responses
• Simple function-based imaging of mAb in the body.
• Simple function-based prediction of for vaccine responses
• New assays to predict antibody effector or immune modulatory functions in mAb productions
• A new antibody engineering strategy that can be adapted to generate new medicines for the treatment of other inflammatory diseases, e.g. lupus
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.