ICF: Chimeric antigen receptor T cells targeting CD123, CD33 and CLL1 for therapy of Acute Myeloid Leukaemia

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Acute myeloid leukaemia (AML) is the commonest aggressive leukaemia in adults and has an increasing frequency with age. Despite advances made in treatments, in general, less than a third of adults survive long-term, though prognosis is better in younger age groups and certain subtypes. The most effective treatments are intensive chemotherapy and bone marrow transplantation which are toxic. A smaller proportion of patients do not survive because the disease does not respond to treatment (a third), a small proportion die due to toxicity and in some the disease responds but then comes back (about half). At this point, patients have often reached the ceiling of doses of certain chemotherapy agents which limits therapy options.A new form of immune therapy for cancer called chimeric antigen receptor (CAR) T cells has been developed. This takes cells which are part of our immune system and through a form of genetic re-programming, can enable them to recognise and kill cancer cells. This is effective in another rarer form of leukaemia (acute lymphoblastic leukaemia) and we are trying to extend this approach to treat AML. This is challenging because the genetically- reprogrammed CAR T-cells also recognise and kill healthy cells such as normal bone marrow cells because they cannot distinguish these cell types. Since bone marrow transplantation is part of the standard care for a fit patient with relapsed AML, but normally involves high dose chemotherapy to clear the host bone marrow and 'make space' for the donor system to seed effectively, we propose to study CAR T cells which are effective against AML and investigate using their 'bone marrow-clearing' properties to set up an effective platform for bone marrow transplantation with lower doses of preparatory chemotherapy. If our CAR T cell therapy works well, it will be a step forward on the path to developing effective CAR T cell treatments and making them available for patients with AML