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

CD21定向CAR-T细胞免疫疗法治疗复发/难治性T细胞急性淋巴细胞白血病（T-ALL）

• 批准号: MR/T000821/1
• 负责人: Martin Pule
• 金额: $ 33.14万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT000821%2F1
• 关键词: CD21; directed; CAR; cell; immunotherapy

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.

t细胞是我们免疫系统中寻找并摧毁感染细胞的细胞。由于癌细胞来自我们自己的组织，t细胞通常不会识别和攻击它们。长期以来，医学一直在寻找一种方法，让我们的免疫系统与癌症作斗争。最近，一项名为“CAR - t细胞疗法”的技术实现了这一目标——从患者的血液中提取t细胞，通过基因工程“重新编程”以识别癌症，然后再注入患者体内。CAR - t细胞疗法在治疗一种被称为b -急性淋巴细胞白血病（B-ALL）的儿童白血病方面非常成功，这种白血病对化疗没有反应。在美国的研究中，CAR - t细胞疗法几乎100%有效，约60%的患者处于缓解期。在伦敦大学学院，我们在GOSH进行了一项名为CARPALL的研究，显示了类似的结果。大约15%的儿童和25%的成人ALL患者患有t型ALL而不是b型ALL。尽管这些白血病是相关的，但T-ALL细胞表面有不同的蛋白质，这意味着目前的CAR疗法不能使用。T-ALL是一种相对罕见的疾病，目前还没有新的治疗方法——尽管进行了非常密集的化疗和骨髓移植，但标准治疗失败的患者预后很差。我们已经在T-ALL癌细胞上发现了一种靶蛋白，我们建议开发一种CAR疗法，使标准治疗失败的儿童和成人T-ALL患者可以接受CAR - t细胞治疗。由于b型all和t型all是相关的，我们相信这种CAR疗法很有可能对t型all起作用。鉴于我们在伦敦大学学院进行的九项开放式CAR研究的经验，我们相信这笔资金将导致第一阶段的研究。