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。威胁生命的主要并发症之一是急性移植物抗宿主病(AGVHD)，供者免疫系统损害患者的皮肤、肝脏和肠道等组织。树突状细胞启动和引导免疫反应。我们已经证明树突状细胞是AGVHD启动的中心，并已经证明在AGVHD出现之前，激活的树突状细胞上表达一种名为CMRF-44的标志物。我们已经开发了针对激活的树突状细胞的潜在的新的治疗性抗体，并表明它们在临床前研究中是有效的。该项目将进一步验证这些抗体，然后测试它们的安全性和预防患者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，即保留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.