Abstract

Optimizing Anti-Cancer Therapy with Immune Stimulatory Antibodies: Big Doors Swing on Little Hinges

Stephen Beers, Professor of Immunology and Immunotherapy, University of Southampton

Clinical successes with immunomodulatory monoclonal antibodies (mAb) have confirmed that the adaptive immune system can produce long-term cures for cancer patients. These remarkable findings with immunomodulatory mAb have, to date, been restricted to checkpoint blockers with their co-stimulatory counterparts failing to translate. Here, data will be presented that illustrates the mechanistic complexity of co-stimulatory mAb targeting 4-1BB (CD137). We will show that these mAb are able to perform multiple functions with opposing Fc?R requirements. Further, we will demonstrate that inappropriate Fc selection can lead to blunted responses that limit efficacy. Finally, once the mechanistic requirements for therapeutic efficacy are established we show that these can be used to design optimal combination therapies and to engineer single agent combination mAb. These data provide a framework for engineering co-stimulatory mAb for clinical translation.