New compounds to fight cancer
Dr Youcef Mehellou, whose research group focusses on proteins called phosphates in cell signalling and drug discovery, has developed a series of molecules that awaken the body’s immune system to fight cancer.
Activating immune cells
The activation of the immune system to attack and eliminate cancer cells and tumours is proving to be an effective strategy for treating this disease.
Dr Mehellou’s research group discovered a series of compounds that are able to selectively target and activate one type of immune cells, which are thought to be important in fighting cancer in humans. This activated sub-type of immune cells was then shown to be effective in eradicating bladder cancer cells.
The research was based on a naturally occurring molecule in bacteria, which is known to activate the immune response in humans. However, this molecule has poor drug-like properties.
To enhance the drug-like properties of this naturally occurring compound, Dr Mehellou and his team designed and made a series of derivatives, now termed 'ProPAgens', of this naturally occurring compound. These new derivatives exhibited potent activation of the immune response, which led to the elimination of bladder cancer cells.
The compounds are a very promising starting point in the development of new immunotherapeutic drugs against many diseases like cancer and tuberculosis. The potency of these compounds in eradicating cancer cells is quite impressive and the team are currently optimising them further in order to study their efficacy and safety in cancer models.
Papers
- Davey MS et al. Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses. Journal of Medicinal Chemistry 2018, 61, 2111-2117.
- Kadri H et al. Aryloxy Triester Phosphonamidates of Phosphoantigens Exhibit Favorable Stability and Potent Activation of Vγ9/Vδ2 T‐Cells. ChemRxiv 2018, DOI: 10.26434/chemrxiv.6755033.v1.
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