This year’s Nobel Prizes were big for cancer science.
First, the Nobel Prize for Physiology or Medicine went to two scientists who laid the groundwork for immunotherapy.
And then came the Nobel Prize for Chemistry. Sharing the prize this year were three scientists: Professor Frances Arnold, Professor George Smith and Professor Sir Gregory Winter.
Arnold was awarded the prize for her research into the directed evolution of enzymes, which has been used to produce biofuels and make the manufacturing of chemicals more environmentally friendly.
The other half of the award went to Smith and Winter “for the phage display of peptides and antibodies”.
It may not be obvious from the name, but phage display has had a huge impact on drug development and is used in many of our drug discovery labs today.
The news was particularly significant for some of our scientists in Cambridge.
“We work two buildings along from MedImmune, which was formerly Cambridge Antibody Technology, the biotech company cofounded by Greg Winter,” says Dr Maria Groves, head of Cancer Research UK – MedImmune Alliance Laboratory (CMAL), where phage display is routinely used.
“When we heard he had won the Nobel Prize, there was a lot of excitement in the lab.”
George Smith and phage display
A phage is a virus that infects bacteria and tricks them into reproducing it.
Back in 1985, Smith saw an opportunity to use this viral trickery in his research. He developed a technique called phage display, which involves modifying the phage’s DNA so that it carries the genetic recipe for a protein molecule.
When the modified phage infects the bacteria, causing that recipe to be read, the protein that’s produced pops out on the surface of the new copies of the virus.
This gloriously simple technique opened countless new avenues of research in labs around the world. It gave scientists a way to link genes to the proteins they produced. And it set in motion a new way to select and evolve proteins.
2018 #NobelPrize laureate George Smith developed a method known as phage display, where a bacteriophage – a virus that infects bacteria – can be used to evolve new proteins. pic.twitter.com/roX8uOFICe
— The Nobel Prize (@NobelPrize) October 3, 2018
And thanks to Sir Gregory Winter, phage display has become a powerful technique to develop drug treatments made from antibodies.
Winter’s antibody wonderland
Antibodies make up a key part of our immune system. But because of their ability to bind to specific targets, they also have huge potential as treatments.
Winter’s work on phage display has helped to refine that potential.
Using phage display, scientists can insert DNA recipes for different shaped antibodies into the phage, creating a library of potential antibodies that will stick to different targets. They can use this library to fish out antibodies that bind most strongly to a drug target.
By repeating this process again and again, scientists can find antibody treatments that precisely stick to the molecule they’re interested in. And for those who use the technology daily, it has allowed them to do their research at a scale that wasn’t possible before.
“Since Winter’s discovery, MedImmune have produced phage display libraries that contain billions of fragments,” says Groves. “These libraries are the key reagents we use to find new antibody therapies.”
The first treatment to be developed using the technique was for rheumatoid arthritis, psoriasis and inflammatory bowel diseases. Since then, phage display has been used to discover cancer treatments like necitumumab, which has been trialled for some people with advanced lung cancer.
“Phage display has transformed medicine,” says Groves. “It’s so exciting that the power of this technique, and its significance to medical science, has been recognised through Sir Greg Winter’s Nobel prize.”