Immunoglobulin E (IgE) antibodies are well known for their role in allergic diseases and for contributions to anti-parasitic immune responses. Properties of this antibody class that mediate powerful effector functions may be redirected for the treatment of solid tumors. This has lead to the rise of a new class of therapeutic antibodies to complement the armamentarium of approved tumour targeting antibodies, which to date are all IgG class. The perceived risk of type I hypersensitivity reactions following administration of IgE has necessitated particular consideration in the development of these therapeutic agents. Here we bring together the properties of IgE antibodies pivotal to the hypothesis for superior anti-tumour activity compared to IgG, observations of in vitro and in vivo efficacy and mechanisms of action, and a focus on the safety considerations for this novel class of therapeutic agent. These include in vitro studies of potential hypersensitivity, selection of and observations from appropriate in vivo animal models and possible implications of the high degree of glycosylation of IgE. We also discuss the use of ex vivo predictive and monitoring clinical tools, as well as the risk mitigation steps employed in, and the preliminary outcomes from, the first-in-human clinical trial of a candidate anti-cancer IgE therapeutic.
- Basophil activation test (BAT)
- In vivo models
- Type I hypersensitivity