Objective

Monoclonal antibodies designed to stimulate anti-tumour immunity by blocking immune checkpoint pathways are achieving remarkable clinical success. However, they are effective in only a portion of patients and additional immune enhancing strategies are required. A second class of therapeutic antibody in development is designed to stimulate immunity by agonising co-stimulatory receptors on antigen presenting cells or effector T cells. Due to their more complex mechanism of action these agents require more sophisticated engineering to achieve function. In this presentation I will review the critical roles of antibody isotype, Fc receptor interactions and epitope specificity in the activity of antibodies directed against co-stimulatory TNFR superfamily members, with a particular focus on CD40.