Blocking the activity of an essential protein to treat T-cell acute lymphoblastic leukaemia

T-cell acute lymphoblastic leukaemia (T-ALL) affects around 200 people per year in the UK, with the vast majority being children and young adults. Treatment includes steroids and chemotherapy, sometimes followed by a stem cell transplantation. These treatments are so toxic that some patients can’t tolerate them, and can result in serious long-term side effects.

They also don’t work for one in five children and around 50% of adult patients – and the cancer can come back after initially successful treatment. When this happens, treatment options are extremely limited. Young people desperately need new medicines that are more effective and less toxic.

Dr Maarten Hoogenkamp’s team at the University of Birmingham have shown that a protein, called EAAT1, is essential to the growth of T-ALL cells. They have developed inhibitors that can ‘switch off’ the protein in the lab, but they need refining before they can be tested further.

In this project, the researchers will be addressing a key issue in their early inhibitors – that they are not able to persist inside the body. They will refine the inhibitor to make it more stable in the body, so it can’t be broken down as quickly.  

Their new, more stable EAAT1 inhibitors will then be tested on mice with T-ALL to confirm their stability and ability to slow or eliminate the cancer. This is a crucial step that can show the safety and efficacy needed to eventually move the inhibitors forward to clinical trials.

Dr Vesna Satulovic will be performing the laboratory work as the senior postdoc on the project.