PHASE IB TRIAL OF INTRAPERITONEAL GM-CSF

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人类单核细胞 从外周血收获的细胞可以在体外活化， 过继性转移到患者的腹膜腔中， 腹膜癌病和这种治疗癌症的方法 可能具有有限的功效。 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腔内注射 腔 先前在小鼠中的研究表明， 这将导致大量的招聘， 单核细胞和巨噬细胞进入腹腔。 如果我们能完成 在人类中，我们可以验证单核细胞和巨噬细胞 可以在人体内引起肿瘤反应。 分为三个部分 研究患者将接受单独的GM-CSF、GM-CSF与干扰素 γ或GM-CSF与白细胞介素-2（IL-2）。 所有的药物都将在 腹腔注射 迄今为止，已有2名患者入组并接受治疗。 我们 单核细胞和粒细胞数量显著增加 在腹膜液中 尚未观察到肿瘤缓解。 因此，在本发明中， 已经确定单核细胞可以被募集到腹膜 腔 需要更多的病人和治疗， 体内单核细胞的活化和体内抗肿瘤活性可以 评估。

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 monocytes harvested from the peripheral blood 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 we can accomplish this in humans we can test the hypothesis that monocytes and macrophages can bring about tumor responses in humans. 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. Two patients have been enrolled and treated so far. We have seen substantial increases in the number of monocytes and granulocytes in the peritoneal fluid. No tumor responses have yet been observed. Thus, it has been determined that monocytes can be recruited to the peritoneal cavity. Additional patients and treatments will be required before activation of monocytes in vivo and antitumor activities in vivo can be assessed.