A team of University of Alberta researchers has created a molecular compound that activates the immune system and shows promise for becoming an effective and versatile treatment for cancer and chronic infections.
"This is a step forward towards developing a small-molecule drug that can help activate the immune system," says Khaled Barakat, professor in the Faculty of Pharmacy and Pharmaceutical Studies and senior author of a recent study published in Medicine in Drug Discovery.
"This could open new avenues for immunotherapy and better patient outcomes."
Small molecules — low molecular weight compounds able to control the function of particular proteins within cells — have the potential to change the way we treat a variety of immunological diseases, Barakat explains. They also have several advantages over current approaches.
Currently, most approaches targeting diseased cells by way of the immune system involve the use of immunostimulants. Like small molecules, these drugs work by stimulating and activating the immune system. They are effective, but there are downsides. Many immunostimulants are very expensive to manufacture and administer, and require high doses. They also typically have a long half-life — the time needed for the amount of the drug in the body to reduce by half — leading to a greater chance of adverse reactions, he says.
Small molecules, on the other hand, are much less costly and have a shorter half-life. They are also more stable at room temperature, and small-molecule drugs are better able to enter into circulation in the body.
They can also cross the blood-brain barrier, a system of specialized cells that protect the brain from toxins in the blood — something most immunostimulants can't do.
"This is one of the big advantages," says Barakat. "If you have a small molecule which can cross the blood-brain barrier, you can actually start treating unreachable tumours."
The small molecule Barakat's team created, named Compound B, is a derivative of another potential compound the group was testing. The difference is that Compound B is more water-soluble than the other compound — a key factor in creating a drug that is effectively absorbed and distributed throughout the body.
In their study, the researchers confirmed that Compound B stimulated the immune cells because they saw an increase in both the amount of T cells (immune cells that target particular antigens, like cancer cells) and the amount of cytokines (small proteins that play a critical role in regulating the immune system).
Zeroing in on promising compounds
As Barakat explains, his lab starts by using machine learning and molecular modelling to narrow down potential compounds to a select few that show promise.
"We do everything you would do in an experiment in the lab, but we do it in the computer."
After their screening process identifies a few compounds of interest, such as Compound B, these are then tested in peripheral blood mononuclear cells (PBMCs). PBMCs contain a variety of immune cells also found in blood, allowing researchers to model the effect they believe the compound will have on the body.
"When you add the compound, it starts to trigger the immune system to secrete certain materials, which indicate that the immune system has become activated," says Barakat.
Research to identify potential targets for Compound B to bind to is already underway and will be the focus of a followup publication.
This interdisciplinary project involves collaborators from the U of A's Mike Petryk School of Dentistry and the departments of chemistry, oncology, biochemistry and medical microbiology and immunology and was funded by the Alberta Cancer Foundation, the Canadian Institutes of Health Research and the Li Ka Shing Applied Virology Institute.
"It is a breakthrough in our group that we're really happy about, and we hope to follow the same procedure in developing new drugs in the future."
