Suppressing auto-reactivity with antibodies that augment inhibitory receptor function - Isis Project No 1475
Researchers at the University of Oxford have devised a new method to inhibit auto-reactivity using antibody superagonists that specifically target inhibitory cell surface receptors reliant on extrinsic tyrosine kinases
Marketing Opportunity
The therapeutic antibody market currently generates 30% of all biotechnology revenues. Most antibodies used as drugs block cellular functions. However, a new class of potentially therapeutic antibodies that augment signalling by cellular receptors is now emerging. These antibodies directly target a class of cell surface receptors ideally suited to changing cellular behaviour because they form an integral part of the tyrosine phosphorylation network of the cell. The activity of these receptors is governed by their phosphorylation state, which appears to be augmented by antibodies that bind the receptors close to the membrane. Since most of these receptors are inhibitory, it should be possible to quench unwanted cellular responses with these antibodies. In the case of the immune system, it is anticipated that antibodies of this type will be useful for switching off chronic auto-reactive T cells. There is an opportunity for collaborative research to assess the effectiveness of these antibodies in animal models with potential for therapeutic applications in various autoimmune diseases, e.g. diabetes and rheumatoid arthritis.
THE OXFORD INVENTION
The Oxford invention consists of a new, general way to design antibodies that augment signalling by receptors dependent on extrinsic tyrosine kinases. Specifically, antibodies are selected that bind close to the membrane and prevent large tyrosine phosphatases from dephosphorylating the receptor. Because receptor dephosphorylation, but not phosphorylation, is disrupted, overall signalling by the receptor is enhanced. Our initial therapeutic target is PD-1, which is expressed specifically on activated B- and T-cells, i.e. in the context of on-going inflammatory responses. The discovery that PD-1 is up-regulated in the context of chronic viral infections and responsible for the exhausted phenotype characteristic of virus-specific T cells, has made it one of the most attractive therapeutic targets in the immune system. The Oxford group has developed an antibody that binds to PD-1 in vitro and in vivo in a membrane-proximal manner, and is therefore expected to switch off autoreactive T cells by imposing an exhausted phenotype on these cells.Patent Status
This work is the subject of a patent application, and Isis would like to talk to companies interested in developing the commercial opportunity that this represents. Please contact the Isis Project Manager to discuss this further.