On behalf of Caner Theme, you are invited to attend our next Cancer Study Group Seminar to be delivered by Dr Debra Josephs, Kings College London as detailed below. Please put the date for this highly informative talk in you diary.
Presentation Title: IgE Immunotherapy of cancer
Speaker: Dr Debra Josephs MRCP PhD, Clinical Lecturer, Medical Oncology, Kings College London, Guy’s Hospital
Time and date: 1-2pm, Friday 23 January 2015
Venue: PRMB 2021 (Doctoral Suite), Penrhyn Road, Kingston University
HOST: Professor Helmout Modjtahedi
Summary: All current antibody cancer therapeutics rely on only one class, namely IgG. Although efficacious, IgG binds with relatively low affinity to immune cell receptors and is subject to inhibitory mechanisms. Other antibody classes, namely IgE, may demonstrate superior tissue bioavailability and higher receptor affinity, which may in turn result in improved efficacy. We have developed MOv18 IgE against the ovarian carcinoma antigen, folate receptor alpha (FRa) in order to model this hypothesis. A safety concern for IgE immunotherapy is induction of effector cell activation (anaphylaxis) in the circulation. In my presentation I will discuss how this has been assessed using two disparate in vitro model systems. I will also discuss my development of an immunocompetent surrogate rat model of FRa-expressing carcinoma (including engineering of surrogate rat-MOv18 IgE and IgG2b antibodies) in order to examine the efficacy and safety of MOv18 IgE. Using this model systemic administration of MOv18 IgE and IgG2b has demonstrated significantly superior efficacy of MOv18 IgE compared to IgG2b. Furthermore, administration of MOv18 IgE for the first time in an animal expressing the full complement of IgE-receptor-expressing immune cells has revealed no additional clinical nor histopathological toxicities compared to IgG2b. These findings are of pivotal significance to the translation of the first IgE class antibody towards first-in-human clinical trials.