CD21 directed CAR-T cell immunotherapy for relapsed/refractory T-cell acute lymphoblastic leukaemia (T-ALL)

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T-cells are cells of our immune system that look for and destroy infected cells. Since cancer cells arise from our own tissues, T-cells do not usually recognize and attack them. Medical science has long sought to find a way to bring our immune system into the fight against cancer. Recently, a technology called "CAR T-cell therapy" has achieved this - T-cells are taken from a patient's blood, "re-programmed" to recognize cancer by genetic engineering and infused back.CAR T-cell therapy has been extremely successful in treating children with a type of leukaemia called B-Acute Lymphoblastic leukaemia (B-ALL) who have failed to respond to chemotherapy. In studies in the US, CAR T-cell therapy has resulted in almost 100% response, with about 60% of patients staying in remission. At UCL, we have a study called CARPALL open at GOSH, which is showing similar results.About 15% of children and 25% of adults with ALL have T-ALL rather than B-ALL. Although these leukaemias are related, T-ALL cells have different proteins on their surface and this means current CAR therapy cannot be used. T-ALL is a relatively rare disease and there are no new treatments on the horizon - patients who have failed standard therapy have a poor prognosis despite very intensive chemotherapy and bone-marrow transplants. We have found a target protein on T-ALL cancer cells against which we propose to develop a CAR therapy so that children and adults with T-ALL who have failed standard treatment can receive CAR T-cells. Since B-ALL and T-ALL are related, we believe there is a good chance that this CAR therapy will work in T-ALL. Given our experience - nine open CAR studies at UCL, we are confident this funding will lead to a phase I study.