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 Frequent blood samples will be withdrawn from the patient or donor over the ensuing 96 hours to determine the rate at which the infused cells equilibrate with the marginating pool of blood monocytes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， 自体单核细胞的数量。 单核细胞将从正常志愿者或癌症中取出 通过细胞分离术和逆流纯化对患者进行治疗 离心淘析 纯化的单核细胞将是 在4度下放置4小时（正常单核细胞）或被激活 通过暴露于重组人γ干扰素 细胞将 用铟-111标记并静脉输注回 正常供体或患者。 正常捐献者还是癌症 患者将首先静脉输注自体 正常单核细胞;如果没有注意到不良反应，则供体 或者患者可以接受自体γ干扰素的输注， 激活单核细胞。 频繁的血液样本将 在随后的96小时内从患者或供体体内撤出 以确定输注的细胞与 血液单核细胞的边集池（如果存在），以及 确定这些细胞从细胞中迁移的速率， 血液进入网状内皮系统和其他 组织中 此外，还将在 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， 将给予纯化的自体细胞毒性血液单核细胞， 癌症患者静脉注射。