From lab-based discovery to global blockbusters
17 Aug 2015
Forty years on from Dr César Milstein and Dr Georges Köhler’s Nature paper describing monoclonal antibodies for the first time, the technique has been applied on an extraordinary scale.
Monoclonal antibody technology is behind a third of all new medicines introduced worldwide and six out of ten of the best selling drugs in the world, demonstrating the importance of lab-based discovery science for finding solutions to medical problems.
Monoclonal antibodies, identical antibodies produced in the lab from rodent cells against one specific target, were invented at the MRC Laboratory of Molecular Biology (MRC LMB) in the 1970s by Dr César Milstein and Dr Georges Köhler.
Researchers had been striving for many years to find a way to make large numbers of tailored, identical antibodies in order to answer basic scientific questions and potentially for clinical applications.
Researchers at the MRC LMB in the late 1980s and early 1990s, including Sir Greg Winter, went on to develop techniques to 'humanise' the rodent antibodies, making them suitable for treating disease. These technologies have been used in the development of over half of marketed antibody therapies today, including the arthritis drug Humira, the multiple sclerosis drug Lemtrada and the breast cancer drug Herceptin.
Millions of patients have been treated with antibody therapeutics, helping them to live with a range of debilitating and often painful conditions. Monoclonal antibody products had global revenues of nearly $75 billion in 2013. From royalties on its ‘antibody portfolio’ the MRC has received more than £580 million. Some of those products have been produced by spin-outs from MRC research and others by licensing to pharmaceutical companies.
The first ‘fully human monoclonal antibody’ to gain approval was adalimumab in 2003. Marketed as Humira (HUman Monoclonal antibody In Rheumatoid Arthritis) it is a treatment for rheumatoid arthritis and other autoimmune conditions. Humira is the world’s top-selling medicine – in 2014 sales reached almost £12 billion, and they are still growing. The MRC, Sir Greg Winter and other LMB scientists, co-founded the spin-out biotechnology company Cambridge Antibody Technology to translate this work to the clinic.
The MRC also funded the research in the late 1980s that developed and humanised the antibody alemtuzumab (Lemtrada), a successful treatment for chronic lymphocytic leukaemia, previously known as Campath. In 2014 it was approved as a treatment for early-stage multiple sclerosis in the US and UK and is making a real impact in the treatment of this difficult and disabling condition 30 years on from its beginnings in the lab.
These successes, and on-going research, are a result of many years of funding and effort by scientists in the UK and around the world. According to Geoff Hale, the co-discoverer of the Campath family of antibodies, more than 2,000 people (from researchers and clinicians to patent lawyers) have been involved in the development of alemtuzumab, as well as the invaluable contribution of the patients who took part in early clinical trials.