PHASE IB TRIAL OF INTRAPERITONEAL GM-CSF

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。各种动物研究也证明了 提示体内单核细胞和巨噬细胞的激活可带来 关于选定模型系统中的肿瘤反应。之前的一项研究 生物反应调节剂计划表明，人类 外周血单核细胞可以在体外和过继激活 腹膜腔内转移者的腹膜功能 这种治疗癌症的方法可能会 疗效有限。在这项研究中，我们将给予重组人 人粒细胞巨噬细胞集落刺激因子 仅限于腹膜疾病的患者的腹膜内注射 空洞。先前在小鼠身上的研究表明，给药 GM-CSF以这种方式将导致大量招募 单核细胞和巨噬细胞进入腹膜腔。如果这能实现的话 在人类身上完成的假设是单核细胞和巨噬细胞 可以在人体内引起肿瘤反应，可以进行测试。在三年内 这项研究的不同部分患者将单独接受GM-CSF， GM-CSF+干扰素-γ或GM-CSF+白介素2(IL-2)。全 药物将通过腹膜腔给药。已经有四名患者被 到目前为止已经登记并接受了治疗。我们已经看到了大幅增长的 腹腔液中单核细胞和粒细胞的数量 病人。没有观察到肿瘤反应。因此，单核细胞可以 将被招募到腹膜腔，但将有更多的患者 体内单核细胞激活和抗肿瘤活性前所需 可以在体内进行评估。

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 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.