Biologics

Biologics, such as monoclonal antibodies and therapeutic proteins, are a can be as potent as manufactured drugs and have added major and growing therapeutic options for the treatment of many diseases. Researchers at UCL are at the forefront of work in this field.

Case study: Rituximab for Rheumatoid Arthritis

Research at UCL has pioneered B-cell depletion to treat Rheumatoid Arthritis (RA) and stimulated the development of B-cell-directed therapies for other autoimmune rheumatic, haematological and neurological diseases.

Now NICE approved (in 2007 updated for 2011), B-cell depletion (based on rituximab) in RA is as effective as the alternative (anti-TNF drugs) and allows effective treatment for patients unable to gain benefit from anti-TNF drugs.

Rituximab offers cost savings of up to £5,000 per patient and is a more convenient option, being given as an infusion at approximately six monthly intervals. B-cell depletion has also proven to be safe, with many receiving repeated courses of treatment. By mid-2013 an estimated 230,000 patients have been treated with rituximab for RA.

Case study: Bench to bedside research into blood vessel formation

A search carried out by Professor John Greenwood and Professor Steve Moss for genes showing abnormal expression in affected blood vessels in the eye, led to a host of interesting hits – and the beginnings of an extensive drug development programme.

Professor John Greenwood

The initial study led to the identification of LRG1, a potent stimulator of new blood vessel formation. Notably, it seemed to have a more important role in the disorganised blood vessel growth seen in eye disease. Following successful project grant funding from the MRC, these effects turned out to reflect LRG1’s action on the well-characterised TGFβ signalling pathway. TGFβ has been implicated in many cellular processes, and its action is highly context-dependent. LRG1 may be one of many factors influencing its action, tilting it in favour of pathogenic angiogenesis.

Aberrant blood vessel formation is seen in several conditions, including the wet form of age-related macular degeneration, the most common form of blindness in older people, and proliferative diabetic retinopathy. Angiogenesis is also a target of several cancer therapies, which block the formation of new blood vessels that tumours need to grow.

With translational funding from the MRC, Professor Greenwood and Professor Moss are now generating a ‘humanised’ LRG1-blocking monoclonal antibody. The work as an archetypal ‘bench to bedside’ project to identify basic mechanisms of disease, to assess the potential to intervene in critical pathways, and to develop targeted interventions. This has the twin benefits of shedding light on critical biological processes – in this case how

new blood vessels are formed – while also generating potential new therapeutic agents.

The project generated a Nature article in July 2013 and has sparked considerable interest from the pharmaceutical industry. With UCLB, Professor Greenwood and Professor Moss are now considering which route to pursue for further commercialisation. The work has also generated a wealth of opportunities for further research, into the mechanisms of blood vessel formation and the action of one of cell biology’s most pivotal signalling pathways.