CD45 ANTIBODY EFFECT ON NORMAL AND MALIGNANT HEMOPOIESIS

描述：(改编自《调查者摘要》)：干细胞 移植可以挽救一些复发或复发的病人。 抗药性白血病，但其他许多人继续屈从于复发的疾病。 本申请中概述的研究将测试两种抗CD45抗体的组合 单抗(MAb)的安全性、生物活性和 复发性急性白血病和CD45+患者的药代动力学特征 将接受同种异体干细胞移植的原始细胞。剂量递增， 从6.25微克/公斤到6400微克/公斤，将允许识别最大耐受量 剂量(MTD)以及产生可识别的生物效应的剂量 病人。这项研究的基本假设是单抗 联合应用将具有抗白血病活性，并将增强植入， 没有与标准调理疗法相关的毒性。因此， 计划进行研究，以确定抗CD45单抗剂量增加的影响 关于正常造血和淋巴细胞、白血病原始细胞和 与历史对照相比，髓系/血小板植入时间没有 接受抗体。在这项为期两年的研究结束时， 将建立抗CD45单抗组合，以及其对正常人的影响 体内的恶性淋巴造血细胞。因为要检测的单抗 依赖宿主效应机制，而不是结合毒素或 放射性核素，重大生物活性的证明将表明 这些单抗作为TEM细胞移植调节剂的潜力。事实上, 根据所提议的研究结果，它们很可能被用作 接受同种异体移植患者的唯一调理剂 非恶性疾病的移植，或基因修饰的自体干细胞。

DESCRIPTION: (Adapted from the Investigator's abstract): Stem cell transplantation can be relied upon to salvage some patients with recurrent or resistant leukemia, but many others continue to succumb to resurgent disease. Studies outlined in this application will test a combination of two anti-CD45 monoclonal antibodies (mAb) for its safety, biologic activity and pharmacokinetic properties in patients with relapsed acute leukemia and CD45+ blast cells who are to receive allogeneic stem cell grafts. Dose escalations, from 6.25 to 6400 mu g/kg, will permit identification of a maximum tolerated dose (MTD) as well as the dose that produces discernable biologic effects in patients. The underlying hypothesis of this research is that the mAb combination will have anti-leukemic activity and will enhance engraftment, without the toxicity associated with standard conditioning regimens. Thus, studies are planned to determine the effects of anti-CD45 mAb dose escalations on normal hematopoiesis and lymphopoiesis, leukemic blast cells and myeloid/platelet engraftment times, as compared with historic controls not receiving the antibodies. By the end of this 2-year study, the safety of the anti-CD45 mAb combination will be established, as will its effects on normal and malignant lymphohemopoietic cells in vivo. Because the mAb to be tested rely on host effector mechanisms rather than conjugated toxins or radionuclides, demonstration of significant biologic activity will indicate the potential of these mAb as tem cell transplant-conditioning agents. In fact, depending on the outcome of the studies proposed, they might well be used as the sole conditioning agent in patients who are to receive allogeneic transplants for nonmalignant disease, or gene modified autologous stem cells.