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- Title
Activation of peritoneal cells upon in vivo transfection with a recombinant alphavirus expressing GM-CSF.
- Authors
Klimp, A H; van der Vaart, E; Lansink, P O; Withoff, S; de Vries, E G E; Scherphof, G L; Wilschut, J; Daemen, T
- Abstract
In this study we determined the in vivo localization of recombinant proteins 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 granulocytemacrophage colony-stimulating factor (rmGM-CSF) on intraperitoneal recruitment and activation of cells. Finally, the therapeutic effect of SFV-GM-CSF treatment on an i.p. growing ovarian tumor was determined. Intraperitoneal injections of recombinant SFV particles encoding the reporter protein luciferase resulted in a high level of luciferase activity in cells of the peritoneal lining and tumor cells in the peritoneal cavity. Low levels of luciferase activity were found in liver, spleen and lungs. Injection of SFV-GM-CSF particles resulted in a slight increase in the number of peritoneal macrophages and in a significant increase in the number of neutrophils. In contrast to multiple i.p. injections with commercially available recombinant GM-CSF, i.p. injected SFVGM-CSF particles activated the macrophages to tumor cytotoxicity. Although treatment of tumor-bearing mice with SFVGM-CSF particles did not result in prolonged survival, tumor growth was inhibited for 2 weeks. Our findings indicate that macrophage-activating cytokines expressed by the efficient and safe recombinant SFV system when administered i.p. may provide an immunotherapeutic treatment modality additional to current chemotherapeutic treatment of intraperitoneally growing cancers.
- Subjects
RECOMBINANT proteins; SEMLIKI Forest virus; GRANULOCYTE-macrophage colony-stimulating factor
- Publication
Gene Therapy, 2001, Vol 8, Issue 4, p300
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301385