MONOCLONAL ANTIBODIES FOR THE TREATMENT OF ACUTE MYELOGE

用于治疗急性脊髓病的单克隆抗体

• 批准号: 3169988
• 负责人: EDWARD David BALL
• 金额: $ 14万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-06-01 至 1989-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3169988
• 关键词: antibody specificity; autologous transplantation; bone marrow transplantation; cell mediated cytotoxicity; cellular oncology; human subject; human therapy evaluation; hybridomas; monoclonal antibody; myelogenous leukemia; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; tissue /cell culture; tumor antigens

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.

该项目涉及治疗的基本和临床方法， 急性骨髓性白血病（AML）使用单克隆抗体细胞毒性， 骨髓性白血病细胞 使用两种单克隆抗体（PM-81和 AML-2-23）以及其他人 我们计划进行一项临床试验， 自体骨髓移植治疗急性髓细胞白血病 净化缓解期病人的骨髓 研究的目的是 提高从缓解期骨髓中清除白血病细胞的能力 通过生产和选择合适的抗体， 有效地解决了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 用单克隆抗体在体外杀死白血病细胞， 考察 此外，我们还将研究细胞表面抗原的表达。 用单克隆抗体体外检测白血病集落形成细胞（L-CFC） 和补体介导的细胞毒性。 将对患者进行连续随访 为了检查细胞表面抗原和L-CFC数据是否 与其对自体骨髓移植的临床反应相关 用单克隆抗体净化 这项研究的另一个方面是发展方法，以丰富和 从骨髓中纯化多能祖细胞，用于基础 研究和移植。 这些将采用单克隆抗体 私家侦探已经准备好了这似乎是反应与许多 包括多能造血祖细胞的祖细胞类别 细胞 我们将尝试利用淘选和细胞分选技术， 使用AML-1-99单克隆抗体纯化祖细胞。 我们建议继续进行单克隆抗体净化的I期研究， 急性髓系白血病患者的骨髓缓解 第二次或第三次缓解。 在实现10个成功的目标后， 移植，证明植入不会被治疗废除 对于单克隆抗体，我们打算开始第二阶段的临床试验， 单克隆抗体净化首次缓解患者的骨髓 与AML。 必须强调的是，所要求的资金用于 这个项目的临床前方面 临床试验的支持是 预计将来自第三方运营商和/或机构开销。 我们提出了大量极其重要的临床前研究， 将大大增加我们对AML细胞生物学的了解。 在 此外，这些研究可能会为患者提供一种上级治疗形式， AML患者，其中大多数人不适合接受同种异体骨髓 移植