Minimising side-effects of drugs for patients with intraocular inflammation In 2013 the UK’s National Institute for Health Research (NIHR) published a list of prioritiesfor eye research based on a national consultation exercise conducted through the JamesLind Alliance. The number one priority for patients with ocular inflammatory diseases was tofind better treatments, and especially to find alternatives to the use of steroid drugs whichare limited by wide-ranging side-effects. We are therefore seeking to develop a new therapythat will minimise the use of steroids in patients with potentially blinding inflammatory eyediseases.Ten years ago, the National Eye Research Centre enabled our research team to be the firstto study the effect of steroids on the immune system of patients with inflammatory eyediseases. This revealed huge variation in peoples’ response to steroids, based on which wehave identified a type of immune cell which escapes the effect of steroids in patients whoexperience the most side-effects of treatment. Our goal is to use a new type of medication toselectively inhibit these steroid resistant cells and therefore minimise the dose of steroidspatients need to control their inflammatory eye disease. To do this we are learning from thefield of cancer medicine which has pioneered the use of a technology called antibody-drugconjugation. This combines the biological precision of an artificially engineered antibody withthe powerful effects of conventional drugs. Such technologies are very novel and they havenot previously been applied to the treatment of inflammatory diseases.We have commissioned a leading UK based biotechnology company which specialises inantibody-drug conjugation (Polytherics Ltd, Abzena Plc) to generate an antibody fragmentwhich attaches to a protein called CCR6 on the surface of steroid resistant immune cells,and to link this to a drug which we have shown strongly inhibits steroid resistant cells. In thisproposal, we are seeking to conduct experiments that will test in principle whether this newdrug conjugate can suppress human steroid resistant cells in the laboratory and also inspecialised mice that have human immune systems. If this is successful we will seek furtherfunding from the UK Medical Research Council for full pre-clinical development of the drugconjugate for inflammatory eye diseases.