A Phase 1 Clinical Trial of a Human Chimeric Anti-Activated DC Antibody to Prevent AGVHD in high risk allo HSCT.

骨髓移植为白血病、淋巴瘤和其他危及生命的血液疾病提供了挽救生命的疗法。急性移植物抗宿主病（AGVHD）是主要的危及生命的并发症之一，在这种情况下，供体免疫系统会损害患者的皮肤、肝脏和肠道以及其他组织。树突状细胞启动并指导免疫反应。我们已经证明树突状细胞是AGVHD发生的核心，并且在AGVHD出现之前，一种名为CMRF-44的标记物在活化的树突状细胞上表达。我们已经开发出针对活化树突状细胞的潜在的新治疗性抗体，并在临床前研究中表明它们是有效的。该项目将进一步验证这些抗体，然后测试它们的安全性和在患者中预防AGVHD的能力。该试验还将测试它们是否具有预期的额外有益效果，即保持保护性的抗病毒和抗白血病免疫反应。

Bone Marrow transplants provide life saving therapy for leukaemias, lymphomas and other life threatening blood disorders. One of the major life threatening complications is acute graft versus host disease (AGVHD) in which the doner immune system damages the patient's skin, liver and gut, amongst other tissues. Dendritic cells initiate and direct immune responses. We have shown that dendritic cells are central to the initiation of AGVHD and have shown that a marker called CMRF-44 is expressed on activated dendritic cells before AGVHD emerges. We have developed potential new therapeutic antibodies that target activated dendritic cells and shown that they are effective in preclinical studies. This project will further validate these antibodies, then test their safety and their ability to prevent AGVHD in patients. The trial will also test whether they have the expected additional beneficial effect of preserving protective anti-viral and anti leukaemic immune responses.