Antibodies: The discovery of Phage Display technology

Former colleagues and grateful patients recount the importance of Greg Winter’s work in discovering Phage Display technology.

Greg Winter won the Nobel Prize in Chemistry in recognition of his work on antibodies at the MRC Laboratory of Molecular Biology (MRC LMB). He realised antibodies all have the same basic structure, with only small changes making them specific for one target. This discovery led to antibody therapies for cancer, and diseases such as rheumatoid arthritis and multiple sclerosis, which have changed the lives of patients across the world. Here, we hear from people who worked with and benefited from Greg’s discoveries.

“Greg had a vision to drive things forward – he encouraged people to think, take risks,” said Peter Jones, who worked at MRC LMB, but is now retired. “Greg realised the way to tackle disease – and, therefore, the future of medicine – was to be in antibodies, and he had been developing new techniques to create them.

“In the early 1980s, work in this area had focused on creating rodent-based antibodies, but the problem was, the human body rejected them after 10 days. Greg thought we should be able to create antibodies that were completely humanised.

“We developed new techniques that were successful but cumbersome, and time-consuming, but Greg knew the possibility was there to create a clinically relevant antibody that would be of use to our friends and neighbours in Addenbrooke’s. So we looked at how the human body develops antibodies, which led to the discovery of Phage Display.

“This provided a way to identify target-binding proteins from millions of different proteins without the need to screen each molecule. It meant we could instantly speed up the process of developing and creating humanised antibodies that could specifically target certain diseases.”

Greg’s work led to the creation of Cambridge Antibody Technology (CAT), where he helped embed a culture of collaboration into the company. Dr Jane Osbourn OBE, chair of Mogrify, who used to work at AstraZeneca, remembers: “The exchange of scientific ideas and sharing of information were pivotal to many of the advances we made in our research and, building on the work Greg started at the LMB, we were able to create world-leading Phage Display libraries.”

These libraries are still in use – and growing – today. CAT, with Greg’s influence, was an ‘early adopter’ and led the way. Says Jane: “The core platform technology that was developed and applied by CAT was ahead of others, but it was a competitive field. Greg helped us understand the importance of publishing scientific papers and of filing patent applications.”

Now, Phage Display technology is used around the world for antibody discovery and remains fundamental to the discovery of biologic medicines. More than 60 potential drugs have been derived using Phage Display in clinical research, and around a dozen are already on the market, treating a wide range of diseases, including inflammatory and respiratory conditions, and cancers.

Theresa Langford worked at the MRC LMB for 29 years, and while she was aware of Greg Winter’s work, she couldn’t have foreseen the impact it would have on her life after she was diagnosed with Sjögren’s Syndrome at 32. “It was a fairly short succession from starting CAT that Humira [a biological medicine used to reduce inflammation by acting on the immune system] was created and I was accepted on a clinical trial that involved a drug called etanercept – part of the family of drugs called ‘The Biologicals’. This was in February 2005.

“On clinical trials, you don’t get told what you are taking, but the first morning I woke after starting my course I knew I was on the real stuff. It was like a magic wand. The swelling from the arthritis and the fatigue just melted away. My life began to get back to relative normality, especially after operations to unblock my tear ducts. I could ride motorbikes and horses again, go camping – I was keen to do everything as my world was opened back up.

“I sometimes wonder what would have happened if etanercept hadn’t been invented – there was nothing else left that was effective or not toxic; I would have gone back to the least bad and plodded on. I would have had a different career path, or not been able to do all the things I wanted to – and it would have been painful and bloody miserable. So I count myself exceptionally lucky it worked."

Greg Winter and Jane Osbourn