POTENTIAL FOR YOUR ANTIBODIES

Therapeutic Antibody Group

MRCT’s Therapeutic Antibody Group collaborates with MRC scientists who have interesting and novel targets that are accessible to monoclonal antibodies or who already have antibodies. Once a potent monoclonal antibody to an accessible target is identified, the Therapeutic Antibody Group converts it to a ‘humanised’ form so that it can be developed into a drug.

Antibody humanisation – essentially genetic modification of rat antibodies to their humanised equivalent – was first invented by Sir Greg Winter at the MRC Laboratory of Molecular Biology in Cambridge . This technology has effectively solved the problem of immune reactions associated with earlier attempts to use mouse antibodies for therapy. Today it is a clinically validated technology. Eleven humanised antibodies are already on the market and more than 70 others are in clinical trials worldwide.

Over the past 18 years Therapeutic Antibody Group scientists have built up a strong record of success in this field, generating 30 humanised antibodies - eight of which have successfully reached clinical trials. This list includes Tysabri® (natalizumab) which recently gained regulatory approval in the US and Europe to treat multiple sclerosis, and Actemra® (tocilizumab) which is currently treating Castleman’s disease in Japan and awaiting approval as a therapy for rheumatoid arthritis.

Drug Discovery Group

MRCT’s Drug Discovery Group consists of integrated biology and medicinal chemistry teams, who work together to find novel chemicals which can be developed into potential drugs or can be used as tools for further research.

The biology group works with MRC scientists and the medicinal chemistry group to identify compounds that interact with specific drug targets, and to supply the support needed to determine proof of concept for particular disease models. Their work includes studying the feasibility of new targets, producing reagents needed for screening, developing assays to test interactions between compounds and potential targets and screening for activity. To date the biology group has completed 12 projects screening high numbers of compounds for activity against potential drug targets. It works closely with academic collaborators at all stages of the process.

MRCT’s medicinal chemistry group has assembled an in-house collection of compounds which is used in screening campaigns to identify those that might be starting points for medicinal chemistry. To develop a strategy for this work, the group examines how the binding of a molecule to a biological target changes as the structure of the molecule is altered: the so-called structure-activity relationship. From this, they try to predict how to improve activity. Molecules which have been designed in this manner are then synthesised and tested, and the results are used to further refine or change their predictions about activity and to improve binding.

As well as improving potency, the medicinal chemists also have to consider the wider issues concerning compounds with the potential to be new drugs. For instance, how well a molecule transfers from the gut into the bloodstream, how stable it is in the blood, how quickly the compound is excreted from the body, whether it will reach the target organ in the body, how long its effects will last and whether it will have any toxic side effects. Many of these factors significantly increase the complexity of designing a new drug. But because the Drug Discovery Group has a strong grounding in pharmaceutical-based medicinal chemistry, it is well positioned to tackle these issues.

Contact Us

Both the Drug Discovery Group and Therapeutic Antibody Group are now looking for new targets for the next generation of small molecule and antibody-based therapies. If you have a potential target that you think might be important, please contact Tarran Jones for TAG enquires (email tarran.jones@tech.mrc.ac.uk) or Katy Kettleborough for DDG enquires (email catherine.kettleborough@tech.mrc.ac.uk), or visit www.mrctechnology.org.