“Engineering Antibodies for Immune Agonism”

Hosts: Dr Henry McSorley, Dr Linda Sinclair & Dr Andy Howden

Venue: Sir Kenneth & Lady Noreen Murray Seminar Room, CTIR 2.84

Abstract  

Agonistic antibodies directed to immunostimulatory receptors are a currently untapped source for immunotherapy. Whereas checkpoint blockers have translated into the clinic, the rules for agonistic antibodies have been more difficult to discern and these reagents await further optimisation. Here we highlight the salient properties of monoclonal antibodies (mAb) required to strongly agonise these receptors and discuss potential strategies for leveraging them for immune activation and anti-tumour efficacy. Using TNFR superfamily receptors as a paradigm the following key aspects will be discussed: The role of isotype; properties of the epitope; the importance of antibody hinge flexibility and the impact of affinity on delivering receptor agonism. 

Biography 

Mark Cragg is Professor of Experimental Cancer Biology in the School of Cancer Sciences at the University of Southampton Faculty of Medicine. He is a member of the Antibody and Vaccine Group, joint Deputy Head of School Research in Cancer Sciences and Director of the MRC DTP in Translational Biomedical Sciences. His research concerns how therapeutics result in tumour regression with a focus on antibodies and small molecules, with a particular interest in Fc receptors and TNFR family members. The aim is to understand how these therapeutics delete tumour cells, how resistance occurs, and how it might be overcome through antibody engineering. 

Throughout the strategy undertaken is highly translational with iterative cycling between in vitro experiments, appropriate in vivo model systems, and primary clinical material. He sits on advisory boards for several charities, institutes and companies and has published over 200 research papers. In 2024, he was made a Fellow of the Academy of Medical Sciences in recognition of his contribution to the development of antibody immunotherapy.