In:
Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2006-06)
Abstract:
Monocyte/macrophages (MO/MA), a polymorphic population of innate immune cells, have the potential to mediate antitumor effects, and may also contribute to protumor effects. A priming and post-chemotherapy schedule of the myeloid cell mobilizing and immune stimulatory growth factor, granulocyte monocyte stimulating factor (GM-CSF, Leukine ® ) and the MO/MA activating cytokine recombinant interferon gamma 1b (rIFN-γ1b, Actimmune ® ) has been developed. The pre- and post-chemotherapy design is based upon known in vivo kinetics and immune modulatory effects of these molecules. Carboplatin (Paraplatin ® ) was selected as the cornerstone of treatment of epithelial ovarian cancer (EOC). Methods We studied hematopoietic and immunologic effects of GM-CSF and rIFN-γ1b before and after carboplatin in patients with recurrent EOC. Potentially chemotherapy-sensitive patients with recurrent measurable tumors received subcutaneous GM-CSF (starting at 400 μg/day) for 7 days plus subcutaneous rIFN-γ1b (100 μg) on days 5 and 7, before and after intravenous carboplatin (area under the curve of 5). We performed standard hematologic assessment and monitored monocyte (MO), dendritic cell, major cell subset counts, and antibody-dependent cell-mediated cytotoxicity (ADCC) against a Her2neu + tumor cell line, as well as selected plasma inflammatory cytokine, chemokine and growth factor levels. Results Our analysis comprised only the first 3 months of treatment in the initial 25 patients. Relative to pretreatment baseline values, white blood cell, neutrophil, MO, and eosinophil counts increased ( P ≤ .001 for each); the proportion of platelets increased 9 days after the second ( P ≤ .002) and third ( P ≤ .04) carboplatin treatments; and the number of cells in the activated MO subsets CD14+HLA-DR+, CD14+CD64+, and CD14 + CXCR3 + increased ( P ≤ .04 for each); plasma levels of the proangiogenic interleukins 1α, 6, and 8 were lower ( P ≤ .03 for each); M-CSF, a product of activated MO/MA, was increased on day 9 ( P = .007); and GM-CSF was increased in plasma after GM-CSF administration ( P ≤ .04). Quality of life measurements were reduced during the GM-CSF/IFN-γ1b cycle while recovering at pre-chemotherapy baseline for FACT-G scores only. Conclusion A novel regimen of GM-CSF plus IFN-γ1b administered to 25 EOC patients receiving carboplatin increased myeloid cells, platelets and total activated MO populations during the initial 3 months; however, ADCC responses were not consistently enhanced during this period.
Type of Medium:
Online Resource
ISSN:
1479-5876
DOI:
10.1186/1479-5876-4-16
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2006
detail.hit.zdb_id:
2118570-0
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