Revolutionizing Anticancer Therapy with Click Chemistry

Researchers at UCL and Stanford University have developed an anti-cancer therapy using “click chemistry”. They were able to create a three component therapy that targets cancer cells. This new approach of using click chemistry for developing cancer immunotherapies opens up new possibilities for future therapeutic advancements. 

Related Article: Three Scientists Jointly Win Nobel Prize for Innovations in Click Chemistry

Advancing Cancer Therapies 

In a study published in Nature Chemistry, scientists used bispecific T cell engagers (BiTEs) to promote the death of cancer cells by bringing the cells close to cytotoxic T cells. Cytotoxic T cells are a type of immune cells that are able to kill foreign cells. They generated three-protein conjugates using click chemistry, a chemical method, and tested their efficacy in vitro. The generated conjugates consist of three components, the first targets cancer cells, and another recruits T cells. Finally, the last component knocks out the cancer cell’s defenses. 

The component that knocks out the cell’s defenses consists of a checkpoint inhibitor, PD-1 blocking antibody, or sialidase enzyme. A PD-1 blocking antibody is used to treat advanced forms of lung and skin cancer. On the other hand, sialidase is an enzyme that strips sialic acids (sugars) from cancer cells’ surfaces. These sugars are generally present in greater amounts in cancer cells than in normal cells, but more importantly, they help cancer cells by switching off approaching immune cells. The therapy they developed that used sialidase was shown to be especially effective at killing breast cancer cells grown in vitro. 

What is Click Chemistry? 

The Nobel Prize in Chemistry for 2022 was awarded to K. Barry Sharpless, Carolyn R. Bertozzi, and Morten Meldal for the development of click chemistry and bioorthogonal chemistry. In click chemistry, chemicals are clicked together to form new molecules, like Lego blocks being put together. These building blocks are able to be joined, or “clicked” together to form desired molecules because they have two click handles that are able to attach to each other without the production of toxic by-products. This allows for the easy creation of molecules with new properties that would otherwise require extensive skills and equipment.  

Click chemistry is a chemical way of generating bispecific antibodies, as opposed to the typically used expression-based methods like protein engineering. Click chemistry has higher reactant specificity and tolerance to functional groups. Additionally, it offers greater modularity, speed, and reproducibility. Dr. Peter Szij, from the Chemistry Department at University College London, 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.” 

Ultimately, the study found that the addition of sialidase improved the efficiency of the therapy against cancer. The next step for the sialidase enzyme therapy would be testing it in animals before it could advance to human trials. The study was supported by Wellcome with funding from the National Institute of Health,  UKRI,  Leverhulme Trust, and the EU’s Horizon 2020 programme. This study showed the untapped potential that using click chemistry to develop future therapies has.

Author

GeneOnline Team