MONOCLONAL ANTIBODIES FOR THE TREATMENT OF ACUTE MYELOGE

该项目涉及基础和临床方法，以治疗 应用细胞毒单抗治疗急性髓系白血病(AML) 髓系白血病细胞。使用两种单抗(PM-81和 AML-2-23)已由首席调查员及其他人员准备 我们打算在这项研究中开发的，我们计划进行一项临床试验 应用单抗治疗急性髓系白血病的自体骨髓移植 净化缓解期患者的骨髓。这些研究是设计的 提高从缓解期骨髓中清除白血病细胞的能力 通过产生和选择适当的抗体 有效解决髓系白血病的抗原异质性问题 细胞。免疫毒素与化疗药物联合应用的疗效观察 用单抗在体外杀死白血病细胞将是 检查过了。此外，我们还将研究细胞表面抗原的表达。 用单抗体外培养白血病集落形成细胞(L-CFCs) 补体介导的细胞毒作用。将对患者进行连续随访 为了检测细胞表面抗原和L-CFCs的数据 与自体骨髓移植的临床反应相关 用单抗净化。 这项研究的另一个方面是开发方法来丰富和 从骨髓中提纯多能祖细胞用于基础研究 研究和移植中。这些细胞将使用一种单抗 已经由私家侦探准备好了，似乎对许多 包括多能造血祖细胞在内的造血祖细胞类别 细胞。我们将尝试利用平移和单元格排序技术 用AML-1-99单抗纯化祖细胞。 我们建议继续我们的第一阶段的单抗净化研究。 急性髓系白血病缓解期患者的骨髓 第二次或第三次减刑。在实现了10个成功目标后 移植，证明植入不会因治疗而被废除 有了单抗，我们打算开始第二阶段的临床试验 单抗净化首次缓解患者的骨髓 急性髓系白血病。必须强调的是，所要求的资金是用于 这项计划的临床前方面。对临床试验的支持是 预计将来自第三方运营商和/或机构管理费用。 我们提出了大量极其重要的临床前研究 将显著增加我们对AML细胞生物学的了解。在……里面 此外，这些研究可能会为患者带来更好的治疗形式。 AML，他们中的大多数不符合异基因骨髓移植的条件 移植。

This project involves basic and clinical approaches to the treatment of acute myelogenous leukemia (AML) using monoclonal antibodies cytotoxic to myeloid leukemia cells. Using two monoclonal antibodies (PM-81 and AML-2-23) already prepared by the Principal investigator, as well as others which we propose to develop in this study, we plan a clinical trial of autologous bone marrow transplantation in AML using monoclonal antibodies to purge bone marrow from patients in remission. The studies are designed to improve the ability to remove leukemia cells from remission bone marrow by producing and selecting appropriate antibodies that deal more effectively with the issue of antigenic heterogeneity on myeloid leukemia cells. The efficacy of immunotoxins and chemotherapeutic agents combined with monoclonal antibodies in killing leukemia cells in vitro will be examined. In addition, we will study the surface antigen expression of leukemia colony-forming cells (L-CFC) in vitro using monoclonal antibodies and complement-mediated cytotoxicity. Patients will be followed serially in order to examine whether the cell surface antigen and L-CFC data correlate with their clinical response to autologous bone marrow transplant with monoclonal antibody purging. Another aspect of this study is the development of methods to enrich and purify pluripotent progenitor cells from bone marrow to use for basic studies and in transplantation. These will employ a monoclonal antibody already prepared by the P.I. which appears to be reactive with numerous classes of progenitor cells including multi-potent hematopoietic progenitor cells. We will attempt to utilize panning and cell sorting techniques to purify progenitor cells using the AML-1-99 monoclonal antibody. We propose to continue our Phase I study of monoclonal antibody purging of remission bone marrow in patients with acute myeloid leukemia who are in second or third remission. After achieving the goal of 10 successful transplants, demonstrating that engraftment is not abrogated by treatment with monoclonal antibodies, we intend to begin a Phase II clinical trial of monoclonal antibody purging of bone marrow from patients in first remission with AML. It is important to emphasize that the funding requested is for the preclinical aspects of this program. Support for the clinical trial is expected to come from third-party carriers and/or institutional overhead. We propose a large number of extremely important preclinical studies that will significantly increase our knowledge of the cell biology of AML. In addition, these studies may lead to a superior form of therapy for patients with AML, the majority of whom are not eligible for allogeneic bone marrow transplantation.