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Enhancing Antibody Agonism

The Opportunity: 

Patented technology that allows manipulation of the disulfide bond configuration of the hinge/CH1 regions to control the activity of mAbs directed against a range of immune receptors. This permits the fine-tuning of biological function.

The Technology: 

Monoclonal antibodies (mAbs) that stimulate anticancer immune responses are proving increasingly effective in cancer treatment, with rising evidence that such responses can be harnessed to provide durable eradication of tumours.

This versatile and patented technology provides the exciting opportunity to engineer clinical reagents with defined, tuneable therapeutic activity regardless of FcɣR expression levels in the local microenvironment.

Through a combination of in vitro and in vivo approaches it is shown that IgG2 hinge and CH1 domains delivers unique FcɣR-independent super-agonistic activity to anti-CD40 antibodies, and that this might also apply to other specificities.

Activity is provided by a structurally constrained conformation due to its unique arrangement of disulfide bonds which confers distinct agonistic (or super agonistic) properties to any antibody of choice.

Intellectual Property: 
Patent Family WO 2015/145360 protecting antibodies containing modified IgG2 domains which elicit agonist or antagonistic properties. National Phase filings in Australia, Canada, China, Europe, Japan and USA.

White et al., Cancer Cell 2015; Conformation of the Human Immunoglobulin G2 Hinge Imparts Superagonistic Properties to Immunostimulatory Anticancer Antibodies.