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Sub-category:
Immunobiology
Category:
Immunobiology and Biologic Therapy
Meeting:
2001 ASCO Annual Meeting
Abstract No:
1095
Citation:
Proc Am Soc Clin Oncol 20: 2001 (abstr 1095)
Author(s):
Francisco J. Hernandez-Ilizaliturri, Elizabeth A. Repasky, Myron S. Czuczman, Roswell Park Cancer Institute, Buffalo, NY.
Abstract:
Rituximab is a chimeric antibody directed against the CD20-antigen found on normal and malignant B-cells. Clinical studies in NHL have demonstrated its efficacy as a single agent or in combination with chemotherapy. Rituximab activity has been associated with CMC, antibody-dependent cellular cytotoxicity and/or induction of apoptosis. GM-CSF and G-CSF have been reported to upregulate CD20 expression in NHL-cell lines. Changes in Rituximab-associated CMC have not been studied in cells pre-treated with GM-CSF/G-CSF. Steroids are part of chemotherapy regimens used against NHL. The effect of steroids on Rituximab activity is uncertain. Objectives: Characterize effects of GM-CSF, G-CSF and MP on Rituximab-associated CMC on NHL cell lines. Material and Methods: 51Cr-labeled Karpas, DHL-4, DHL-10, Ramos and Raji NHL-cells were incubated with GM-CSF, G-CSF or MP prior to treatment with Rituximab at three dose-levels (5mcg/ml, 10mcg/ml and 15mcg/ml) and human complement. 51Cr-release assays were performed and the percentage of lysis was calculated for each cell-line. Differences in CD20 expression were evaluated by flow cytometry. Results: The mean % of 51Cr release was higher in Raji (80.8%+/-0.67), DHL-4 (93.2%+/- 0.6) and Ramos (98.65%+/-1.68) than in DHL-10 (10.7%+/-0.5) or Karpas (20.4%+/-9.6). No differences were noted between the three doses of Rituximab tested. NHL-cells sensitive to Rituximab induced-CMC (Raji, Ramos, and DHL-4) had a higher CD20 expression than those with a lesser degree of CMC-killing (DHL-10 and Karpas). Pre-treatment with G-CSF or GM-CSF did not affect CMC; however, MP significantly reduced Rituximab induced-CMC. Decrease in mean % of lysis in MP pre-treated cells were: Karpas (80%), DHL-10 (79.5%), Ramos (66.7%), DHL-4 (27%) and Raji (13.2%). Conclusions: Pre-treatment of NHL-cells with GM-CSF or G-CSF does not increase CMC. However, pre-treatment with MP is associated with variable reduction in CMC. The sequence of administration of Rituximab with chemotherapy (especially steroids-containing regimens) may impact antibody induced anti-tumor activity.
Associated Presentation(s):
Other Abstracts in this Sub-Category:
Abstracts by Francisco J. Hernandez-Ilizaliturri:
Presentations by Francisco J. Hernandez-Ilizaliturri:
Educational Book Manuscripts by Francisco J. Hernandez-Ilizaliturri:
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