A potent anti-cancer therapy has been created using Nobel prize-winning “click chemistry”, in a new study by University College London (UCL) and Stanford University researchers.
The study, published in Nature Chemistry, opens up new possibilities for how cancer immunotherapies might be built in future.
The research team created an anti-cancer therapy with three components: one targeting the cancer cell, another recruiting T cells to attack the cancer cell, and a third knocking out part of the cancer cell’s defences. Previously, this type of three-component therapy has only been built using protein engineering.
One of the therapies, which used an enzyme called sialidase to strip away sugars that the cancer cell uses to hide itself, was especially effective at killing breast cancer cells in a dish. The researchers said this showed that the enzyme has the potential to be the basis of next-generation anti-cancer agents.
First author Dr Peter Szijj (UCL Chemistry) said: “Click chemistry is a quicker and more adaptable way to build these multifunctional anti-cancer agents than protein engineering. It’s relatively easy to attach click ‘handles’ to proteins so you can try lots of combinations quickly to test what might work best. Using protein engineering, you need a separate mechanism for each component.”
New modality for cancer therapy
Click chemistry relies on two reaction partners (click handles) that can attach to each other very rapidly and selectively, without the production of any toxic by-products. These click handles can be added to proteins, in this case using functionalised pyridazinediones (PDs), allowing the proteins to click neatly together.
Carolyn Bertozzi of the Stanford School of Humanities and Sciences, who is a study co-author, was one of three winners of the Nobel Prize in Chemistry in 2022. She said: “This new construct that brings an enzyme building block into the CiTE format has potential as a new modality for cancer immune therapy.”