Could a medicine called ONC-201 help treat children with T-cell acute lymphoblastic leukaemia?

Project title: Pharmacological targeting of the mitochondrial serine protease, ClpP for T-cell acute lymphoblastic leukaemia therapy

Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Nick Jones, Swansea University
Award: £230,943.21
Awarded February 2024

T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive type of blood cancer that affects children. It happens when normal immune cells, called T-cells, do not develop properly and grow uncontrollably. One of the first treatment options for children with T-ALL is chemotherapy.

Some of the most successful chemotherapy drugs target cancer cells’ ability to process nutrients from the diet for growth. However, these drugs also damage healthy cells, leaving children with long-term side effects and compromised quality of life. There is an urgent need to find kinder drugs to treat childhood leukaemia.

ONC-201 is a drug that can target a cancer cell’s metabolism without harming healthy cells.  It is being tested in a clinical trial to treat a type of childhood brain cancer, and is a promising treatment option.

It works by activating a protein in the mitochondria (where a cancer cell makes the energy and building blocks it needs). Once this protein is turned on, it chews up the mitochondria’s machinery. This stops the mitochondria from producing energy and building blocks, which cancer cells rely on for their growth and survival. As ONC-201 does not affect healthy cells, it has very mild side effects.

Dr Nick Jones, at Swansea University, wants to find out whether ONC-201 could be used to treat T-ALL. As the drug is already in clinical trials for other cancer types, it could be repurposed for leukaemia more quickly and cheaply than developing a new drug.

This project has three aims:

  1. To understand how ONC-201 stops T-ALL cells from growing
  2. To test the effects of ONC-201 on T-ALL cells taken from patients
  3. To see how the drugs work in T-ALL models in the lab

Another benefit of repurposing ONC-201 for T-ALL treatment is that the drug is able to get to the brain. This could mean it is useful for treating children whose leukaemia has gone to the brain - this is often very difficult to treat. Dr Jones hopes this project will support the development of a clinical trial testing ONC-201 as a safer treatment for childhood T-ALL.