Why IgE?

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. The epsilon constant region of IgE binds very tightly to its cognate receptor (FcεRI) on the surface of immune effector cells including macrophages, monocytes and basophils. This interaction is up to 10,000 fold greater than the affinity the gamma chain of IgG has for its equivalent receptor. Such tight binding means that, unlike IgG, IgE can remain on the surface of effector cells in the absence of antigen. This makes IgE an ‘anticipatory’ receptor, ideal for cancer immuno-surveillance.

The combination of higher constant region receptor binding and unique cytokine/chemokine expression allows IgE to generate significantly enhanced ADCP (antibody-dependent cell-mediated phagocytosis) and ADCC (antibody-dependent cell-mediated cytotoxicity), the two main mechanisms by which antibodies can kill tumour cells.

Due to its role in killing tissue-born parasites, IgE is able to increase the tissue penetration of immune effector cells such as macrophages, monocytes and basophils. This activity arises from the unique cytokine signature generated by FcεRI activation including high levels of TNFα and the chemokine MCP-1. The images below show that IgE allows superior macrophage permeation of tumours versus an IgG comparator.