Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2006-04-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/4/1/16 |
| _version_ | 1811244522548494336 |
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| author | Patenia Rebecca S Gallardo Stacie T Ramirez Pedro T Levenback Charles F Gordon Ilyssa O Bassett Roland L Cohen Lorenzo Vadhan-Raj Saroj Apte Sachin M Garcia Michael E Iyer Revathy B Freedman Ralph S |
| author_facet | Patenia Rebecca S Gallardo Stacie T Ramirez Pedro T Levenback Charles F Gordon Ilyssa O Bassett Roland L Cohen Lorenzo Vadhan-Raj Saroj Apte Sachin M Garcia Michael E Iyer Revathy B Freedman Ralph S |
| author_sort | Patenia Rebecca S |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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<sup>®</sup>) and the MO/MA activating cytokine recombinant interferon gamma 1b (rIFN-γ1b, Actimmune<sup>®</sup>) has been developed. The pre- and post-chemotherapy design is based upon known <it>in vivo </it>kinetics and immune modulatory effects of these molecules. Carboplatin (Paraplatin<sup>®</sup>) was selected as the cornerstone of treatment of epithelial ovarian cancer (EOC).</p> <p>Methods</p> <p>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<sup>+ </sup>tumor cell line, as well as selected plasma inflammatory cytokine, chemokine and growth factor levels.</p> <p>Results</p> <p>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 (<it>P </it>≤ .001 for each); the proportion of platelets increased 9 days after the second (<it>P </it>≤ .002) and third (<it>P </it>≤ .04) carboplatin treatments; and the number of cells in the activated MO subsets CD14+HLA-DR+, CD14+CD64+, and CD14<sup>+</sup>CXCR3<sup>+ </sup>increased (<it>P </it>≤ .04 for each); plasma levels of the proangiogenic interleukins 1α, 6, and 8 were lower (<it>P </it>≤ .03 for each); M-CSF, a product of activated MO/MA, was increased on day 9 (<it>P </it>= .007); and GM-CSF was increased in plasma after GM-CSF administration (<it>P </it>≤ .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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-04-12T14:26:34Z |
| format | Article |
| id | doaj.art-a125159287c3457fa766110c73ca87ae |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T14:26:34Z |
| publishDate | 2006-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-a125159287c3457fa766110c73ca87ae2022-12-22T03:29:25ZengBMCJournal of Translational Medicine1479-58762006-04-01411610.1186/1479-5876-4-16Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatinPatenia Rebecca SGallardo Stacie TRamirez Pedro TLevenback Charles FGordon Ilyssa OBassett Roland LCohen LorenzoVadhan-Raj SarojApte Sachin MGarcia Michael EIyer Revathy BFreedman Ralph S<p>Abstract</p> <p>Background</p> <p>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<sup>®</sup>) and the MO/MA activating cytokine recombinant interferon gamma 1b (rIFN-γ1b, Actimmune<sup>®</sup>) has been developed. The pre- and post-chemotherapy design is based upon known <it>in vivo </it>kinetics and immune modulatory effects of these molecules. Carboplatin (Paraplatin<sup>®</sup>) was selected as the cornerstone of treatment of epithelial ovarian cancer (EOC).</p> <p>Methods</p> <p>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<sup>+ </sup>tumor cell line, as well as selected plasma inflammatory cytokine, chemokine and growth factor levels.</p> <p>Results</p> <p>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 (<it>P </it>≤ .001 for each); the proportion of platelets increased 9 days after the second (<it>P </it>≤ .002) and third (<it>P </it>≤ .04) carboplatin treatments; and the number of cells in the activated MO subsets CD14+HLA-DR+, CD14+CD64+, and CD14<sup>+</sup>CXCR3<sup>+ </sup>increased (<it>P </it>≤ .04 for each); plasma levels of the proangiogenic interleukins 1α, 6, and 8 were lower (<it>P </it>≤ .03 for each); M-CSF, a product of activated MO/MA, was increased on day 9 (<it>P </it>= .007); and GM-CSF was increased in plasma after GM-CSF administration (<it>P </it>≤ .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.</p> <p>Conclusion</p> <p>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.</p>http://www.translational-medicine.com/content/4/1/16 |
| spellingShingle | Patenia Rebecca S Gallardo Stacie T Ramirez Pedro T Levenback Charles F Gordon Ilyssa O Bassett Roland L Cohen Lorenzo Vadhan-Raj Saroj Apte Sachin M Garcia Michael E Iyer Revathy B Freedman Ralph S Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin Journal of Translational Medicine |
| title | Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin |
| title_full | Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin |
| title_fullStr | Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin |
| title_full_unstemmed | Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin |
| title_short | Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin |
| title_sort | cytokines gm csf and ifnγ administered by priming and post chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin |
| url | http://www.translational-medicine.com/content/4/1/16 |
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