A new study led by researchers at the University of Oxford and Imperial College London has tested a modified immunotherapy approach for treating high-risk childhood leukaemia. Acute lymphoblastic leukaemia is the most common cancer in children, with standard treatments curing about 80% of cases. However, for infants and children with high-risk forms, cure rates remain around 50%. Current therapies such as CAR-T immunotherapy use engineered versions of a patient’s own immune cells but require weeks to prepare due to their personalised nature.
The research team, headed by Professors Anindita Roy and Thomas Milne from the MRC Molecular Haematology Unit and Professor Anastasios Karadimitris at Imperial College London, evaluated a therapy called CAR-iNKT. Unlike traditional CAR-T therapy, CAR-iNKT uses invariant natural killer T (iNKT) cells derived from healthy donors. These cells can be produced in advance and stored, making them available “off-the-shelf.” This approach could be crucial for rapidly progressing cases where immediate treatment is necessary.
The development of this therapy was supported by Cancer Research UK and Children with Cancer UK. Researchers engineered CAR-iNKT cells to target two markers on high-risk leukaemia cells—CD19 and CD133—at the same time. In mouse models, this dual-target method resulted in complete eradication of leukaemia cells, with mice remaining free of disease. By contrast, standard CAR-T therapy only provided temporary remission before the cancer returned.
According to findings published in Blood journal, the new therapy also eliminated leukaemia that had spread to challenging areas such as around the brain, bone marrow, and spleen. Relapse due to cancer persisting near the brain is a significant problem in high-risk childhood leukaemia.
Dr Natalina Elliott, Postdoctoral Researcher in the Childhood Leukaemia Research Group at Oxford’s Department of Paediatrics and co-first author on the study said: "We have found that targeting two markers on the leukaemia cells using CAR-iNKT therapy is more efficient at clearing cancer cells in mice than with CAR-T, even when it has spread to the brain. Reassuringly, we also did not find evidence of major toxicity in our preclinical models even when using high doses of the CAR-iNKT cells. The next step would be to take this therapy to patients."
Senior author Professor Anindita Roy stated: "Cure rates for high-risk infant and childhood leukaemia lag behind standard risk childhood leukaemia. There is an urgent need to develop more effective treatments for this vulnerable patient population in order to prevent relapse, and we were very grateful to receive a Children and Young People’s Cancer Innovation award from Cancer Research UK and Children with Cancer in 2021 to develop a novel immunotherapy.
"Along with our collaborators, we have developed and tested CAR-iNKT cells that target leukaemia cells with high efficiency. The fact that these CAR-iNKT cells can be used off-the-shelf means we can treat high-risk patients upfront without any delay. I am very excited about the clinical implications of this novel immunotherapy."
The full results are detailed in ‘Off-the-shelf’ dual CAR-iNKT cell immunotherapy eradicates medullary and leptomeningeal high risk KMT2A-rearranged leukemia', published in Blood.