Activation of peritoneal cells upon in vivo transfection with a recombinant alphavirus expressing GM-CSF

In this study we determined the in vivo localization of recombinant protein s expressed by intraperitoneally (i.p.) injected recombinant Semliki Forest virus (SFV) particles. Subsequently, we investigated the influence of i.p. administered SFV particles encoding recombinant murine granulocyte-macroph age colony-stimulating factor (rmGM-CSF) on intraperitoneal recruitment and activation of cells. Finally, the therapeutic effect of SFV-GM-CSF treatme nt on an i.p. growing ovarian tumor was determined Intraperitoneal injectio ns of recombinant SFV particles encoding the reporter protein luciferase re sulted in a high level of luciferase activity in cells of the peritoneal li ning and tumor cells in the peritoneal cavity. Low levels of luciferase act ivity were found in liver, spleen and lungs. Injection of SFV-GM-CSF partic les resulted in a slight increase in the number of peritoneal macrophages a nd in a significant increase in the number of neutrophils. In contrast to m ultiple i.p, injections with commercially available recombinant GM-CSF, i.p . injected SFV-GM-CSF particles activated the macrophages to tumor cytotoxi city. Although treatment of tumor-bearing mice with SFV-GM-CSF particles di d not result in prolonged survival, tumor growth was inhibited for 2 weeks. Our findings indicate that macrophage-activating cytokines expressed by th e efficient and safe recombinant SFV system when administered ip. may provi de an immunotherapeutic treatment modality additional to current chemothera peutic treatment of intraperitoneally growing cancers.