PHASE IB TRIAL OF INTRAPERITONEAL GM-CSF

腹膜内 GM-CSF 的 IB 期试验

• 批准号: 3752480
• 负责人: B L GAUSE
• 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/3752480
• 关键词: ascites; clinical trials; colony stimulating factor; combination cancer therapy; combination chemotherapy; granulocyte; human subject; human therapy evaluation; human tissue; injection /infusion; interferon gamma; interleukin 2; leukocyte activation /transformation; leukocytosis; monocyte; neoplasm /cancer chemotherapy; peritoneal fluid; peritoneum neoplasm; recombinant proteins

Monocytes and macrophages can be activated with a variety of cytokines to kill tumor targets in vitro. A variety of animal studies have also suggested that activation of monocytes and macrophages in vivo can bring about tumor responses in selected model systems. A previous study at the Biological Response Modifiers Program suggested that human peripheral blood monocytes can be activated in vitro and adoptively transferred into the peritoneal cavity of patients wit peritoneal carcinomatosis and that this approach to the treatment of cancer may have limited efficacy. In this study we will administer recombinant human granulocyte macrophage colony stimulating factor (rHuGM-CSF) intraperitoneally to patients with disease primarily involving the peritoneal cavity. Previous studies in mice have suggested that administering GM-CSF in this fashion will result in the recruitment of large numbers of monocytes and macrophages into the peritoneal cavity. If this can be accomplished in humans, the hypothesis that monocytes and macrophages can bring about tumor responses in humans can be tested. In three separate parts of this study patients will receive either GM-CSF alone, GM-CSF with interferon-gamma (IFN-gamma), or GM-CSF with interleukin-2 (IL-2). All drugs will be administered intraperitoneally. Twelve patients have been enrolled and treated so far. We have seen substantial increases in the number of monocytes and granulocytes in the peritoneal fluid of eight patients. In addition, there has been evidence of a systemic leukocytosis. No tumor responses have been observed, although ascites resolved in one patient with colon cancer. Thus, monocytes can be recruited to the peritoneal cavity, but additional patients will be required before activation of monocytes in vivo and antitumor activities in vivo can be assessed.

单核细胞和巨噬细胞可以被多种细胞因子激活， 体外杀伤肿瘤靶点。 各种动物研究也 表明体内单核细胞和巨噬细胞的激活可以带来 在选定的模型系统中的肿瘤反应。一项先前的研究在 生物反应调节剂计划表明， 血液单核细胞可以在体外活化并过继转移到 腹膜癌转移患者的腹膜腔， 这种治疗癌症的方法可能具有有限的功效。 在 本研究将给予重组人粒细胞巨噬细胞 集落刺激因子（rHuGM-CSF）腹腔注射给患者 主要累及腹膜腔的疾病。 既往研究 小鼠已经表明，以这种方式施用GM-CSF将导致 在募集大量单核细胞和巨噬细胞进入 腹腔 如果这可以在人类身上实现， 单核细胞和巨噬细胞可以引起人类的肿瘤反应 可以测试。 在本研究的三个独立部分中，患者将 接受单独的GM-CSF、GM-CSF与干扰素-γ（IFN-γ），或 GM-CSF与白细胞介素-2（IL-2）。 所有的药物都将在 腹腔注射 到目前为止，已招募并治疗了12名患者。 我们已经看到单核细胞数量的大量增加， 8例患者的腹腔液中有粒细胞。 此外，本发明还提供了一种方法， 有证据表明全身性白细胞增多 无肿瘤缓解 已经观察到，虽然腹水解决了一个病人的结肠 癌 因此，单核细胞可以被募集到腹膜腔，但 在单核细胞活化之前， 可以评估体内和体内抗肿瘤活性。