BIODISTRIBUTION AND TRAFFICKING OF NORMAL AND ACTIVATED BLOOD MONOCYTES

正常和活化血液单核细胞的生物分布和贩运

• 批准号: 3916664
• 负责人: J W SMITH
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916664
• 关键词: autologous transplantation; cell migration; human subject; human tissue; interferons; intravenous administration; monocyte; neoplasm /cancer immunotherapy; radiotracer

This research study is designed to assess the trafficking pattern of autologous monocytes when given intravensously to humans. Monocytes will be removed from normal volunteers or from cancer patients by cytapheresis and purified by counter-current centrifugal elutriation. The purified monocytes will either be left at 4 degrees (normal monocytes) for 4 hours or be activated by exposure to recombinant human gamma interferon. The cells will be labeled with Indium-111 and infused intravenously back into the normal donor or patient, respectively. Normal donors or cancer patients will first be given an intravenous infusion of autologous normal monocytes; if no untoward reactions are noted, the donors or patients may receive infusions of autologous gamma interferon- activated monocytes four weeks later. Frequent blood samples will be withdrawn from the patient or donor over the ensuing 96 hours to determine the rate at which the infused cells equilibrate with the marginating pool of blood monocytes (if one exists), and to determine the rate at which these cells emigrate from the bloodstream to enter the reticuloendothelial system and other tissues. In addition, multiple regional scintigraphs will be obtained to determine if these labeled monocytes preferentially localize to any one organ system. This information will further our understanding of the normal physiology of activated and unactivated monocytes and, in addition, hopefully will allow us to more rationally design adoptive immunotherapy trials in which purified autologous cytotoxic blood monocytes will be given to cancer patients intravenously.

本研究旨在评估贩运模式 当静脉给予人类时，自体单核细胞的数量。 将从正常志愿者或癌症中取出单核细胞 患者通过细胞分离术并通过逆流纯化 离心淘析。 纯化的单核细胞将是 4度（正常单核细胞）放置4小时或被激活 通过暴露于重组人γ干扰素。 细胞会 用 Indium-111 标记并静脉输回 分别为正常供体或患者。 正常捐献者或癌症 患者首先会接受自体静脉输注 正常单核细胞；如果没有发现任何不良反应，捐赠者 或者患者可能会接受自体γ干扰素输注 四周后激活单核细胞。 频繁的血液样本会 在接下来的 96 小时内从患者或捐赠者体内撤出 确定输注细胞与平衡的速率 血单核细胞的边缘池（如果存在），并且 确定这些细胞从细胞迁移的速率 血液进入网状内皮系统和其他 组织。 此外，还将进行多个区域闪烁扫描仪 获得以确定这些标记的单核细胞是否优先 定位于任何一个器官系统。 这些信息将进一步 我们对激活和正常生理学的理解 未激活的单核细胞，此外，希望能让我们 更合理地设计过继免疫治疗试验，其中 纯化的自体细胞毒性血单核细胞将被给予 癌症患者静脉注射。