Innovative Off-the-Shelf Immunotherapy Offers Hope for High-Risk Childhood Leukemia

Scientists from the University of Oxford, in collaboration with researchers at Imperial College London and the University of Glasgow, have developed a groundbreaking immunotherapy that could significantly improve treatment outcomes for infants and children battling high-risk leukemia. Acute lymphoblastic leukemia (ALL) remains the most common childhood cancer, with current therapies curing about 80% of cases. However, the prognosis for infants and children with the high-risk form of the disease is less optimistic, with cure rates around 50%. Traditionally, high-risk cases are treated with CAR-T immunotherapy, which involves customizing a patient’s immune cells to target leukemia, but this individualized process can take weeks, which is critical in rapidly progressing cases.

The new approach, called CAR-iNKT therapy, introduces a different type of immune cell known as invariant natural killer T (iNKT) cells. Unlike CAR-T cells, which are derived from patients, CAR-iNKT cells can be sourced from healthy donors and prepared in advance, making them an 'off-the-shelf' solution. This ready availability is especially crucial in high-risk situations where swift intervention can make a difference.

In preclinical tests involving mice, the research team engineered CAR-iNKT cells to target two specific markers on leukemia cells—CD19 and CD133. This dual targeting strategy proved highly effective, with mice showing complete eradication of leukemia cells and remaining leukemia-free thereafter. Compared to standard CAR-T therapy, which often results in temporary remission and relapse, CAR-iNKT therapy demonstrated more durable responses.

Further, the therapy was effective against leukemia cells that had invaded critical areas such as the brain's surrounding space, as well as other difficult sites like the bone marrow and spleen—common relapse locations in children. The study, published in the journal Blood, suggests that CAR-iNKT cells could reduce relapse rates and improve long-term survival.

Dr. Natalina Elliott, a co-first author from the University of Oxford, highlighted the therapeutic’s efficiency and safety profile in preclinical models, emphasizing its potential to move into clinical trials. Senior researcher Professor Anindita Roy pointed out the significant gap in treatment success between high-risk and standard leukemia cases and expressed optimism about the clinical potential of off-the-shelf CAR-iNKT cells. Supported by grants from Cancer Research UK and Children with Cancer, this innovative therapy could revolutionize treatment for vulnerable pediatric patients, offering a rapid, effective, and less personalized alternative to existing therapies.