PHASE I TRIAL OF TNF AND GM-CSF

TNF 和 GM-CSF 的 I 期试验

• 批准号: 3752523
• 负责人: J E JANIK
• 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/3752523
• 关键词: CD antigens; clinical trials; colony stimulating factor; combination cancer therapy; combination chemotherapy; dendritic cells; human subject; human therapy evaluation; human tissue; neoplasm /cancer; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; receptor expression; tumor necrosis factor alpha

The purpose of this protocol is to examine the toxicity and immunomodulatory activity of the combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) in patients with advanced cancer. The combination of GM-CSF and TNF stimulate the maturation of dendritic cells from CD34+ bone marrow progenitor cells. TNF has a two-fold function in the maturation of dendritic cells, it up-regulates the expression of the GM-CSF receptor on bone marrow progenitors and prevents their maturation into granulocytes. Dendritic cells are the most potent antigen presenting cells of the immune system. They function as initiators in organ transplant rejection, major histocompatibility restricted T cell responses and in the formation of antibodies dependent on T cells. Dendritic cells are found in small numbers in many tissues and in the peripheral blood. This study will examine the activity of TNF and GM-CSF to stimulate the maturation and function of dendritic cells. Bone marrow will be examined for the presence of dendritic colony forming units before therapy and following each course of therapy. The number of dendritic cells in peripheral blood mononuclear preparations will be examined before and during therapy. Finally, the number of S100+ and CD1A+ cells in skin biopsy specimens will be quantitated. Langerhans cells, a type of dendritic cell, is positive for these markers. The major goal of this protocol is to determine whether the combination of GM-CSF and TNF cause maturation of dendritic cells and increases their number in the blood bone marrow and skin and to determine whether this increase produces tumor regressions.

该方案的目的是检查毒性和 粒细胞-巨噬细胞组合的免疫调节活性 集落刺激因子（GM-CSF）和肿瘤坏死因子（TNF） 晚期癌症患者。 GM-CSF 和 TNF 的组合 刺激 CD34+ 骨髓中的树突状细胞成熟 祖细胞。 TNF 在成熟过程中具有双重功能 树突状细胞，上调 GM-CSF 受体的表达 骨髓祖细胞并阻止其成熟为粒细胞。 树突状细胞是免疫系统中最有效的抗原呈递细胞 系统。它们充当器官移植排斥反应的引发者，主要 组织相容性限制了 T 细胞反应和形成 抗体依赖于T细胞。树突状细胞存在于小 许多组织和外周血中的数量。 这项研究将 检查 TNF 和 GM-CSF 的活性，以刺激成熟和 树突状细胞的功能。 将检查骨髓 治疗前和治疗后存在树突集落形成单位 每个疗程。 外周血中树突状细胞的数量 在治疗前和治疗期间将检查单核制剂。 最后，皮肤活检标本中S100+和CD1A+细胞的数量将 被量化。 朗格汉斯细胞（一种树突状细胞）呈阳性 对于这些标记。 该协议的主要目标是确定 GM-CSF和TNF联合是否导致树突成熟 细胞并增加其在血液、骨髓和皮肤中的数量，并 确定这种增加是否会导致肿瘤消退。