Using synthetic antibodies to treat diffuse midline gliomas

Diffuse midline gliomas (DMGs) are incurable childhood brain tumours, where current treatment gives only temporary relief for most patients. Unfortunately, decades of clinical trials haven’t been able to find a treatment that can improve survival. Recently, immunotherapy has become a powerful tool in treating various forms of cancer. It relies on using antibodies to target cancer cells. However, these antibodies have a number of disadvantages which mean that they are not always very effective.  

The research team at Leicester University, led by Dr Sergey Piletsky, plan to create a new treatment for DMG based on a new technology they have developed, called "synthetic-antibodies". These can be a lot better than the standard antibodies, not least because they can cross the blood-brain barrier that protects the brain. Synthetic-antibodies are very small particles engineered to bind to specific proteins on the surface of cells. In this project the researchers will produce synthetic-antibodies that only bind to a specific protein found only on the surface of DMG cancer cells and not on healthy brain cells. The synthetic-antibodies will also be loaded with drugs that can kill the cancer cells. When these drug loaded antibodies come into contact with the DMG cells they will bind to the protein on the cell surfaces. This will then let the antibodies enter the cancer cells and release their drugs inside, killing only the DMG cancer cells. 

Using a technology created by the Piletsky group in collaboration with the Wellcome Trust and Royal society, the researchers will attach fluorescent molecules to the synthetic-antibodies. This will allow the research team to see whether the antibodies are binding to the protein and if they are able to enter the cancer cells. If this pilot study is successful, Dr Sergey Piletsky hopes to apply for further funding to research the synthetic-antibodies’ effectiveness and their ability to cross the blood-brain barrier.