London scientists have created a potent anti-cancer therapy using “click chemistry”, where molecules click together like Lego bricks.
Researchers at University College London (UCL) and Stanford University say the new technique could open up possibilities for how cutting-edge cancer immunotherapies might be built in future.
Click chemistry works when small molecules are snapped together to form larger and more complex ones. It has been used to directly target tumour cells.
The Nobel Prize in Chemistry was awarded to three scientists from the US and Denmark in October last year for their role in pioneering click chemistry. Carolyn Bertozzi, a chemistry professor at Stanford and a co-author on the UCL paper, was among the three recipients of the prize.
For their study, the UCL team created an anti-cancer therapy with three components: one targeting the cancer cell, another recruiting a white blood cell called a T cell to attack the cancer cell, and a third knocking out part of the cancer cell’s defences.
Scientists first clicked two antibody fragments together - one binding to a cancer cell, another binding to a T cell so that it would destroy the cancer cell.
A third component was then added, a checkpoint inhibitor, which removes an aspect of a cancer cell's defences.
This component was either a PD-1-blocking antibody fragment, used to treat advanced skin or lung cancer; or an enzyme called sialidase, which strips away specific sugars on the surface of the cancer cell. These sugars are produced in large amounts by cancer cells and help them to evade our immune system by switching off approaching immune cells.
The research team found that adding either of these components improved the cancer-killing efficiency of the therapy, and that adding sialidase was especially potent. Sialidase has been found to be particularly effective at killing breast cancer cells in a dish.
Previously, this type of three-component therapy has only been built using a complex process called protein engineering, in which DNA sequences for multiple proteins are combined and inserted into a single cell.
In the study, published in Nature Chemistry, the researchers said that using chemistry in this way to create cancer therapies showed “much untapped potential that is still waiting to be uncovered”.
Senior corresponding author Professor Vijay Chudasama, of UCL, said the technique uncovered by the team was a quicker and more efficient way to build anti-cancer agents than protein engineering.
“As proteins are large and complex molecules, you require a combination of precise protein modification and reliable click chemistry to attach them together in a controlled manner.”
The treatment will be tested in animals before any human trials can begin.
