Monoclonal IgE for solid tumor Immunotherapy
The immunoglobulin E (IgE) is a class of antibody that is capable of triggering a robust immune response resulting in anaphylaxis, which plays a central role in allergic reactions against environmental agents and immunity against parasites. Multiple studies also suggest that IgE also plays a role in cancer immunosurveillance. For example, relevant epidemiological studies on the association of allergies with cancer support a lower cancer risk among people with a history of allergies. Antibodies of IgE class isolated from pancreatic cancer was shown to mediate cytotoxicity against targeted cancer cells. In addition, levels of polyclonal IgE directly correlated with the overall survival in patients with multiple myeloma. All these observations imply that this class of antibody can be exploited for the treatment of cancer to complement the IgG class that has traditionally been developed for cancer therapy.
IgE also has several intrinsic advantages that may increase its therapeutic potential compared to IgG including the exceptionally high affinity for its Fc receptors and its low serum concentration that provide less competition to effector cells involved in tumor killing mechanism. Interestingly, IgE binds cells in tissue as well as in circulation and will home to tumor stroma. Antitumor effects of IgE have been reported in several model system in the literature and at Advanced Immune Therapeutics, Inc., a company (AIT) founded by Dr. Christopher Nicodemus, M.D. FACP from who OncoQuest recently acquired this technology.
Proprietary research done at AIT has established that IgE is capable of inducing potent cross presentation of tumor antigens allowing strong cellular immunity to form against targeted tumor antigens. Additionally, by mobilizing potent direct cellular cytotoxic effectors mechanisms of the allergic inflammatory response, carefully targeted IgE monoclonal antibodies are capable of directly attacking cancer cells including solid tumors. These effects are both induced at concentrations which are lower than required for monoclonal IgGs currently in clinical use. Safe administration of this class of monoclonal antibody has also been demonstrated in primates. The collaboration of AIT with Professor Manuel Penichet of UCLA has also led to some proprietary rights to this technology for OncoQuest.
OncoQuest has initiated a preclinical program in collaboration with Dr. Michael Hollingsworth at University of Nebraska Medical Center to identify a lead product candidate that may be advanced to clinical trial for the treatment of solid malignancy.