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F U L L T E X T P R I M A L S O U R C E : Nature
T I T L E : Comprehensive in vitro characterization of PD-L1 small molecule inhibitors
U of A researcher Khaled Barakat with the IBM supercomputer his team used to develop a small molecule that could help the body fight cancer by allowing the immune system to attack tumours. Credit: Faculty of Pharmacy and Pharmaceutical Sciences
Imagine cancer treatment without chemotherapy, radiation or surgery. Just a small aspirin-like pill.
Sound like magic? That's because it kind of is, according to Khaled Barakat, a University of Alberta biophysicist searching for innovative immunotherapies that could help knock out multiple types of cancer simply by empowering the immune system.
"We used the word 'magic' because the concept is not related to a certain type of cancer," Barakat said. "This will try to fix any problem in the body related to any type of cancer."
Four years ago, Barakat announced the search for a "magic drug" thanks to a $5.4-million partnership with the Alberta Cancer Foundation and the Li Ka Shing Applied Virology Institute. With the help of a supercomputer and a dream team of cancer researchers, Barakat's team has published a new study in Scientific Reports revealing a tiny molecule that could do just that.
"It's a very potent molecule," said Barakat. "It actually proves the concept. And thanks to a massive team effort, we're also making very good progress on another molecule for a different target."
Small molecules, big promise
Cancer attacks the body by co-opting immune checkpoints, molecular "brakes" that normally help the body prevent an overactive immune response. By producing an abundance of these checkpoints, cancer leaves T cells unable to attack the growing tumour.
"Think of the immune system as police," Barakat said. "This is exactly cancer. There's no police. All the cells will eventually transform from normal cells."
The idea of using the immune system to fight cancer has shown a lot of promise.
In recent years, researchers have honed in on antibodies that override these "brakes" and reactivate the T cells. Research on two of these checkpoints, with an estimated therapeutic value worth billions of dollars, won a Nobel Prize in 2018. But although lives have been extended and discernible evidence of the disease has been wiped out for some patients, the approach hasn't been without complications.
Because antibodies are large molecules, they can remain in the body for months, increasing the likelihood that the immune system turns on itself, targeting organs and tissues. Treatments also tend to be extremely expensive and difficult to administer.
Barakat's lab has spent the past four years using an IBM Blue Gene/Q supercomputer—the equivalent of 60,000 desktop computers—to help engineer small molecules that could boost the immune system without harmful side-effects. The molecules are then synthesized and evaluated in real life by a diverse group of U of A researchers including chemists, immunologists, virologists and biochemists.
The new study singles out one of the most promising leads, a compound that turns on the immune system like an antibody used to treat melanoma by targeting the PD-1 checkpoint. Barakat said a second lead compound is under development that would target a different checkpoint known as CTLA-4.
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Edited by Engadin, 08 October 2019 - 06:45 PM.
