Abstract

Summary Venom derived cysteine-rich miniproteins (knottins) have potential as therapeutic agents to block ion channels but suffer from manufacturing difficulties, short half-lives and a lack of specificity. We have developed a novel molecular format wherein the CDR loop of an antibody has been replaced by a knottin. This format, termed a KnotBodyTM, combines the benefits of both scaffolds with the antibody gaining the functionality of a scaffold pre-disposed to the blockade of ion channels and the knottin enjoying the extended half-life and the additional specificity conferred by the antibody molecule. This presentation illustrates the generation of KnotBody molecules with a particular focus on the generation and optimisation of KnotBody inhibitors of the Kv1.3 channel , an important target affecting function of T effector memory cells.

Biography Affiliated Professor John McCafferty was one of the founders of Cambridge Antibody Technology (CAT) and a co-inventor of antibody phage display. In 2012 he formed IONTAS who generated multiple drug leads currently in clinical trial by partner companies. John also developed KnotBodyTM technology to address ion channels, an important target class which are under-served by biologics. He founded Maxion Therapeutics to take advantage of this drug development opportunity. Interspersed with company formation John has held academic positions at the Wellcome Trust Sanger Institute and is currently is an Affiliated professor at the Department of Medicine at the University of Cambridge

Host Prof Mark Wills, Department of Medicine