Making immunotherapy more powerful for high-risk acute leukaemia 

The most common cancer in children is a type of blood cancer called acute leukaemia, and there are two main types: lymphoid (ALL) and myeloid (AML). Some of these leukaemias are harder to treat than others and are called high-risk leukaemias. Often leukaemias that have an abnormality in a gene called KMT2A (KMT2Ar) fall in this category. The overall aim of this project is to investigate whether we can boost the efficiency of the immune cells called iNKT cells, which are programmed to kill KMT2Ar leukaemia cells. 

Our previous research and the preliminary work we generated in support of this application make us hopeful that we will develop a type of treatment called ‘iNKT Cell Immunotherapy’ that will surpass existing immunotherapies and eradicate high-risk infant and childhood acute leukaemia. 

The proposed work will provide proof that ‘boosted’ iNKT and CAR-iNKT cells can eradicate leukaemia cells. If this is proven to be the case, we will work with our commercial partners, Arovella Therapeutics to take our research to the next phase that will include safety testing and development of clinical trials for infants and children with high-risk AML and ALL. 

The concepts addressed in this research proposal are likely to be applicable to other blood cancers. 

Demonstrating the ability of our iNKT based immunotherapy to eradicate KMT2A-r leukaemia in the lab will be the first step towards developing the treatment for patients with acute leukaemia. This will require additional commercial or academic funding and further testing to show it is safe. Overall, assuming availability of additional funding, it will take 3-4 years after the end of the proposed research before it is tested in patients. The immediate benefit will be understanding whether we can make iNKT immunotherapy more effective against leukaemia. Longer term benefits will be to patients with high-risk leukaemia by making a more effective and less toxic treatment available.