Abstract B46: Immunotherapy of solid tumors with IgE antibodies: Paradigm of a novel concept towards clinical application.

Developing therapeutic antibodies with enhanced effector functions may be key to improving clinical outcomes in cancer. Our strategy to address this entails engineering antibodies directly targeting tumor antigens and bearing Fc regions of the IgE antibody class. Numerous attributes of this class, such as natural immune activatory functions in tissues and high affinity for cognate receptors on frequently tumor-resident effector cells can translate into effector cell activation and superior protection against solid tumors, compared to the conventionally-used antibodies with IgG Fc regions. We have developed a paradigm for this concept, the antibody MOv18 IgE, against the tumor antigen Folate Receptor α. This agent is presently prepared for first-in-man clinical studies, having demonstrated superior efficacy compared to the corresponding IgG1 antibody in three in vivo models of cancer, including one in an immunocompetent host. The antibody also yielded very promising safety profiles in in vivo evaluations, and also in ex vivo readouts normally applied in the field of allergy to examine sensitivity to allergens. The latter studies, conducted using cancer patient blood, suggest that this antibody is unlikely to trigger Type I hypersensitivity in patients. We have now extended the pathway to the design of similarly potent antibodies for the treatment of other solid tumors such as malignant melanoma and breast carcinoma. Two antibodies with Fc regions of the IgG1 and IgE classes and the same specificity for CSPG4, a tumor antigen expressed by 80% of melanomas, were tested in a xenograft model of human melanoma in a humanized host, with evident superior efficacy for the IgE counterpart. On-going evaluations and planned clinical studies in patients with cancer will constitute important metrics of the concept of IgE antibodies in cancer therapy, will inform the emerging field of AllergoOncology and will provide new scope for the design of novel cancer therapies. Citation Format: Sophia N. Karagiannis, Debra H. Josephs, Panagiotis Karagiannis, Louise Saul, Amy E. Gilbert, Tihomir Dodev, Alexander Koers, Philip J. Blower, Andrew J. Beavil, Frank O. Nestle, James F. Spicer, Hannah J. Gould. Immunotherapy of solid tumors with IgE antibodies: Paradigm of a novel concept towards clinical application. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B46.