IGEM Therapeutics is a UK Immuno-Oncology company developing novel IgE antibodies to treat cancer. IgE has evolved to kill tissue-dwelling multicellular parasites endowing it with several key features that make it ideal for the treatment of solid tumours which also mostly reside in tissue. The epsilon constant region of IgE binds very tightly to its cognate receptor (FcεRI) on the surface of immune effector cells including macrophages, monocytes, basophils and eosinophils. This interaction is up to 10,000 fold greater than the gamma chain of IgG has for its equivalent receptor and this results in the majority of IgE molecules being permanently attached to the surface of immune effector cells. The latter are therefore primed and ready to destroy cells expressing the antigen recognised by the IgE. As a result, IgE is able to permeate tissues more effectively than IgG and stimulate significantly greater levels of both ADCP (antibody-dependent cell-mediated phagocytosis) and ADCC (antibody-dependent cell-mediated cytotoxicity), the two main mechanisms by which immune effector cells can kill tumour cells. IgE also has a significantly longer tissue half life than IgG (2 weeks versus 2 – 3 days) which also suits it for a role in the destruction of solid tumours.
The company’s lead programme targets the folate receptor alpha (FR alpha) and an anti-FR alpha IgE antibody is currently in a phase 1/2a trial to treat ovarian cancer. This is the world’s first IgE therapeutic to enter the clinic.
IGEM is also developing a novel antibody platform technology based on protein and glyco-engineering of the epsilon constant region.