PHASE IB TRIAL OF INTRAPERITONEAL GM-CSF

腹膜内 GM-CSF 的 IB 期试验

• 批准号: 3853306
• 负责人: R G STEIS
• 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/3853306
• 关键词: antineoplastics; cellular immunity; clinical trials; colony stimulating factor; combination cancer therapy; drug administration routes; human subject; human therapy evaluation; human tissue; immunomodulators; interferons; interleukin 2; leukocyte activation /transformation; macrophage; monocyte; neoplasm /cancer immunotherapy; passive immunization; peritoneal cavity; peritoneum neoplasm

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 with 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 limited to 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, or GM-CSF with interleukin-2 (IL-2). All drugs will be administered intraperitoneally. Four 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 three patients. No tumor responses have been observed. 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被多种细胞因子激活 在体外杀死肿瘤靶点。 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。 先前的一项研究， 生物反应调节剂计划表明， 外周血单核细胞可以在体外和过继性激活 转移到腹膜炎患者的腹腔内， 癌病，并且这种治疗癌症的方法可以 功效有限。 在这项研究中，我们将给予重组 人粒细胞巨噬细胞集落刺激因子 仅限于腹膜疾病的患者腹膜内给药 腔 先前的小鼠研究表明， GM-CSF以这种方式将导致招募大量的 单核细胞和巨噬细胞进入腹腔。 如果这可以 在人类中完成，假设单核细胞和巨噬细胞 能在人体内产生肿瘤反应的方法。 在三 该研究的不同部分患者将接受单独的GM-CSF， GM-CSF与干扰素-γ，或GM-CSF与白细胞介素-2（IL-2）。 所有 将通过腹膜内施用药物。 四名患者已经 到目前为止，治疗和治疗。 我们看到， 腹腔液中单核细胞和粒细胞的数量 患者 未观察到肿瘤缓解。 因此，单核细胞可以 将被招募到腹膜腔，但将有更多的患者 体内单核细胞活化前所需的抗肿瘤活性 可以在体内进行评估。