In 2013 the UK’s National Institute for Health Research (NIHR) published a list of priorities
for eye research based on a national consultation exercise conducted through the James
Lind Alliance. The number one priority for patients with ocular inflammatory diseases was to
find better treatments, and especially to find alternatives to the use of steroid drugs which
are limited by wide-ranging side-effects. We are therefore seeking to develop a new therapy
that will minimise the use of steroids in patients with potentially blinding inflammatory eye
diseases.

Ten years ago, the National Eye Research Centre enabled our research team to be the first
to study the effect of steroids on the immune system of patients with inflammatory eye
diseases. This revealed huge variation in peoples’ response to steroids, based on which we
have identified a type of immune cell which escapes the effect of steroids in patients who
experience the most side-effects of treatment. Our goal is to use a new type of medication to
selectively inhibit these steroid resistant cells and therefore minimise the dose of steroids
patients need to control their inflammatory eye disease. To do this we are learning from the
field of cancer medicine which has pioneered the use of a technology called antibody-drug
conjugation. This combines the biological precision of an artificially engineered antibody with
the powerful effects of conventional drugs. Such technologies are very novel and they have
not previously been applied to the treatment of inflammatory diseases.

We have commissioned a leading UK based biotechnology company which specialises in
antibody-drug conjugation (Polytherics Ltd, Abzena Plc) to generate an antibody fragment
which 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 this
proposal, we are seeking to conduct experiments that will test in principle whether this new
drug conjugate can suppress human steroid resistant cells in the laboratory and also in
specialised mice that have human immune systems. If this is successful we will seek further
funding from the UK Medical Research Council for full pre-clinical development of the drug
conjugate for inflammatory eye diseases.