PHASE I TRIAL OF TNF AND GM-CSF

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 巨噬细胞集落刺激因子和肿瘤坏死因子 晚期癌症患者。巨噬细胞集落刺激因子与肿瘤坏死因子的联合应用 刺激CD34+骨髓来源的树突状细胞成熟 祖细胞。肿瘤坏死因子在肿瘤细胞成熟过程中具有双重作用 树突状细胞，它上调巨噬细胞集落刺激因子受体表达 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提呈细胞。 系统。它们是器官移植排斥反应的始发者，梅杰 组织相容限制性T细胞反应及其形成 抗体依赖于T细胞。树突状细胞见于小细胞 在许多组织和外周血液中都有。这项研究将 检测肿瘤坏死因子和粒-巨噬细胞集落刺激因子的活性，以刺激成熟和 树突状细胞的功能。将对骨髓进行检查以确定 治疗前和治疗后树突状细胞集落形成单位的存在 每一个疗程的治疗。外周血中树突状细胞的数量 单核细胞制剂将在治疗前和治疗期间进行检查。 最后，皮肤活检标本中S100+和CD1a+细胞的数量将 被量化。朗格汉斯细胞是一种树突状细胞，呈阳性 为了这些记号笔。该协议的主要目标是确定 联合应用GM-CSF和肿瘤坏死因子是否能诱导树突状细胞成熟 细胞，并增加它们在血液、骨髓和皮肤中的数量 确定这种增加是否会导致肿瘤退化。

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.