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

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 BRMP suggested that human peripheral blood monocytes can be activated in vitro and adoptively transferred into the peritoneal cavity of pts. with peritoneal carcinomatosis and that this approach to the treatment of cancer may have limited efficacy. In this study we administered rHuGM-CSF intraperitoneally to pts. 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 3 separate parts of this study pts. received either GM-CSF alone, GM-CSF with IFN-gamma, or GM-CSF with IL-2. All drugs were administered intraperitoneally. 14 pts. have been enrolled and treated so far. We have seen substantial increases in the number of monocytes and granulocytes in the peritoneal fluid of 8 pts. In addition, there has been evidence of a systemic leukocytosis. No tumor responses have been observed, although ascites resolved in 1 pt. with colon cancer. Thus, monocytes can be recruited to the peritoneal cavity, but additional pts. would be required before activation of monocytes in vivo and antitumor activities in vivo can be assessed.