Autologous chimeric antigen receptor T cells targeting CCR9 for the treatment of T acute lymphoblastic leukaemia

T细胞急性淋巴细胞性白血病(T-ALL)是一种罕见的急性白血病。大约一半的T-ALL患者可以通过化疗成功治疗。然而，对于化疗后残留或治疗后复发的患者，目前还没有有效的治疗方法。最近，一种新型的癌症治疗方法被开发出来，称为嵌合抗原受体T细胞疗法，或简称CAR-T细胞疗法。T细胞是来自我们免疫系统的细胞。它们的工作是在我们的身体周围移动，寻找并杀死感染病毒的细胞。CAR-T细胞是从患者血液中提取的T细胞，并使用基因工程对其进行重新编程，以便识别癌细胞。当它们点滴回到患者体内时，它们在患者体内生活和生长，发现并杀死癌细胞。CAR-T细胞疗法对包括一种常见类型的急性白血病在内的某些癌症患者很有效，但尚未用于T-ALL。这是因为T-ALL是一种由正常T细胞发展而来的白血病。识别任何T细胞的CAR-T细胞最终会自杀或杀死正常的T细胞，如果没有这种细胞，患者很快就会受到严重感染。我们发现，一种名为CCR9的蛋白质只在白血病T细胞中存在。我们已经开发出识别CCR9的CAR-T细胞。CCR9 CAR-T细胞杀死T-ALL细胞，但不识别正常T细胞。我们建议在难治性T-ALL患者的初步临床研究中检测CCR9 CAR-T细胞。如果CCR9 CAR-T细胞在临床研究中工作良好，这将是使CCR9 CAR-T细胞更广泛地应用于T-ALL患者的第一步。

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.