Sir Gregory Winter has spent the past quarter of a century at his Cambridge University lab working with existing antibodies, adapting nature’s immune mechanism to produce a new generation of innovative drugs.
Working at the other end of the design spectrum, David Baker, a biochemist at the University of Washington, has been using computer models and crowdsourcing to create protein structures from scratch, hoping they will become future vaccines and diagnostic tools.
Both research pioneers were in Toronto this week, where they spoke at a symposium of the Gairdner Foundation about the promises of genetic engineering.
Sir Gregory, 62, is one of this year’s recipients of the Canada Gairdner International Awards, which have a record for predicting future Nobel Prize winners.
His career has been a steady pursuit of ever smaller, more efficient ways to harness the antibody mechanism to fight illnesses. He was a pioneer in engineering humanized antibodies, then focused on domain antibodies, the active parts of antibodies. He now focuses on bicycle peptides, even tinier protein rings that can travel where larger antibodies can’t.
In an interview about new advances in antibody-based biologic drugs, Sir Gregory mentioned the great potential of new drugs that deal with a body mechanism known as the programmed death receptor 1.
The PD-1 acts as a checkpoint on the immune system to prevent it from overwhelming healthy cells. Scientists believe that tumours co-opt the PD-1 to protect themselves. A new class of drugs called checkpoint inhibitors is now revolutionizing cancer therapy by disabling the tumour’s hold on the PD-1.
“It’s like souping up your immune system and your immune system now starts attacking the tumour … It’s going to be very exciting,” Sir Gregory said.
His previous work has been credited with creating the techniques used for cancer drugs such as Avastin and Herceptin. He then helped develop Humira, a drug for rheumatoid arthritis that is becoming one of the biggest-selling medications ever.
Those drugs don’t come cheap, however, and there have been controversies when governments balked at footing the bills for therapies like Herceptin. At the same time, the industry may be at a crossroads because many patents on biologic drugs are now expiring. Because of those drugs’ complex nature, U.S. and Canadian regulators have imposed tougher guidelines for generic drug makers. Health Canada uses the term “subsequent-entry biologic” to indicate that it does not consider biosimilars a generic drug that can be quickly approved without clinical trials.
“If the regulators were more sensible and allowed generics to come in rather than putting up all sorts of hurdles, then in fact you’d have cheaper antibodies,” Sir Gregory said.
While Sir Gregory worries about the patents on the engineering of existing antibodies, Dr. Baker, 51, is still at the experimental phase, designing synthetic proteins from scratch.
Instead of “waiting a billion years for natural selection to solve” today’s medical problems, he hopes that “if you build from the bottom up, you can build a protein structure that’s perfectly tailored to solving your problem.”
His research team has designed a protein that latches onto the flu virus and keeps it from infecting cells. Other projects are looking at ways to fight cancer, malaria and Alzheimer’s disease.
Since Dr. Baker’s work involves computer design, the public has been enlisted with two crowdsourcing initiatives. The first, Rosetta@home, is a program that 350,000 volunteers have downloaded on their home computers. It calculates possible protein structure permutations, using moments when the volunteers’ computers are idle.
Rosetta gave birth to FoldIt, a computer game where volunteers can try to suggest their own protein structures. About 200 people are regular players and some designs have made it into academic studies, Dr. Baker said.