A new type of immune therapy—CAR-T cells engineered to recognise the protein CCR9—is being tested in patients with incurable T cell acute lymphoblastic leukaemia (T-ALL). This matters because roughly half of T-ALL patients relapse after chemotherapy, and no effective treatments exist for them. Standard CAR-T therapy, which works well in other leukaemias, has been unusable in T-ALL because the cancer arises from T cells themselves: CAR-T cells that target any T cell would kill each other and destroy the patient’s healthy immune system. The researchers discovered that the protein CCR9 appears only on leukaemic T cells, not on normal T cells. They have built CAR-T cells that recognise CCR9, and in lab tests these cells kill T-ALL cells while sparing healthy T cells. If this initial clinical study shows that CCR9 CAR-T cells are safe and effective, it would be the first step toward making this therapy available for patients with relapsed T-ALL. Success could transform a disease with no treatment options into one that might be controlled or cured by a patient’s own reprogrammed immune cells.
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T cell acute lymphoblastic leukaemia (T-ALL for short) is a rare type of acute leukaemia. About half of patients with T-ALL can be successfully treated with chemotherapy. However, there are no effective treatments for patients whose disease remains after chemotherapy or which comes back after treatment. Recently, a new type of cancer treatment called "Chimeric Antigen Receptor T cell therapy" or "CAR-T cell therapy" for short, has been developed. T cells are cells from our immune system. Their job is to move around our bodies finding and killing cells infected with a virus. CAR-T cells are T cells taken from a patient's blood and "re-programmed" using genetic engineering so that they recognise cancer cells. When returned to the patient in a drip, they live and grow within the patient,finding and killing cancer cells. CAR-T cell therapy works well in patients with certain cancers including a common type of acute leukemia, but has not been used in T-ALL. This is because T-ALL is a leukaemia which develops from normal T cells. CAR-T cells which recognise any T cell would end up killing themselves or killing normal T cells, without which a patient would quickly suffer from severe infections. We have found that a protein called CCR9 is only found in leukaemia T cells. We have developed CAR-T cells which recognise CCR9. CCR9 CAR-T cells kill T-ALL cells but do not recognise normal T cells. We propose to test CCR9 CAR-T cells in an an initial clinical study in patients with incurable T-ALL. If CCR9 CAR-T cells work well in the clinical study, this would be the first step in making CCR9 CAR-T cells more widely available for patients with T-ALL.
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