Scientists at the University of Oxford, together with colleagues at Imperial College London and the University of Glasgow, have developed a new type of immunotherapy that could improve outcomes for infants and children with high-risk leukemia.

Acute lymphoblastic leukemia is the most common cancer in children. While about 80% of children are cured with current treatments, cure rates for infants and children with high-risk forms of the disease remain about 50%. These patients are often treated with a therapy called CAR-T immunotherapy, which uses engineered versions of a patient’s own immune cells to fight cancer cells. This treatment is highly personalized, but can take weeks to prepare.

In this study, the research team, led by Professors Anindita Roy and Thomas Milne at the MRC Molecular Hematology Unit and Professor Anastasios Karadimitris at Imperial College London, tested a modified therapy called CAR-iNKT. This modified therapy uses a different type of cell to the standard CAR-T therapy called invariant natural killer cells (iNKT cells), which can be created from healthy donors and stored in advance, making them “off-the-shelf.”

Having treatment readily available in this way can be especially important in high-risk leukemia in children, where the cancer may be rapidly progressing.

For the new therapy, researchers engineered CAR-iNKT cells to recognize two markers together on the high-risk leukemia cells called CD19 and CD133. This two-target approach was highly effective when tested in mice; leukemia cells were completely eradicated and mice remained free of leukemia. In comparison, standard CAR-T therapy could only remove leukemia for a few weeks before it returned.

The study, published in the journal Blood, demonstrated that CAR-iNKT therapy was able to remove leukemia cells that had invaded the space around the brain, as well as other difficult-to-treat sites such as the bone marrow and spleen. Blood cancer remaining in the space around the brain is one of the reasons for relapse from high-risk leukemia in children. This may indicate a possible treatment to ensure that children are kept cancer-free for longer.

Dr. Natalina Elliott, Postdoctoral Researcher in the Childhood Leukemia Research Group at the University of Oxford’s Department of Pediatrics and co-first author, said, “We have found that targeting two markers on the leukemia 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 said, “Cure rates for high-risk infant and childhood leukemia lag behind standard risk childhood leukemia. 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 leukemia 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.”