Effects of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) on proliferation and cytokine secretion of immune cells in malignant pleural effusion

Autor: Wolfgang Schuette, Horst Lindhofer, H. Friccius-Quecke, H. Friccius Quecke, Rainer Wiewrodt, Martin Sebastian, Alexander Schmittel, Philipp Kiewe, B. Mueller, M. Jaeger
Rok vydání: 2007
Předmět:
Zdroj: Journal of Clinical Oncology. 25:3046-3046
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2007.25.18_suppl.3046
Popis: 3046 Background: The trifunctional antibody catumaxomab specifically binds EpCAM+ tumor cells, CD3+ T lymphocytes and accessory cells via FcγR I/III. Thus the antibody induces tumor specific cell mediated cytotoxicity in vitro and in vivo. Following last years’ ASCO presentation on a phase I/II trial showing safety and efficacy of repetitive intrapleural administration of catumaxomab in patients with EpCAM positive, malignant pleural effusion (MPE), we now present data on the responsiveness of immune cells from pleural fluid to catumaxomab. Methods: Pleural fluid of patients with EpCAM-positive MPE treated with i.pl. catumaxomab was collected before treatment. Cells were harvested from the fluid and cultured ± 100 ng/ml catumaxomab using an in vitro proliferation assay. After 72 h of culture, proliferation of T cells (CD4+ and CD8+) and monocytes (CD11c+) was determined. In addition, cell supernatants after 24h incubation ± catumaxomab were analysed for their TH1/TH2 cytokine profile (IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF- a). Results: Incubation in presence of catumaxomab led to a pronounced increase of CD4+ CD8+ and CD11+ cell numbers indicating a proliferation of these cells, whereas cultures without catumaxomab showed no proliferation of immune cells. Analysis of supernatants after 24 h revealed levels of IL-2, IL-6, IFN-γ and TNF-a, from cells incubated with catumaxomab that were distinctly higher than in cultures without catumaxomab. Conclusions: The immunologic nature of catumaxomab-induced responses in patients with pleural effusion accompanied by a reduction of tumor cells, could be underlined impressively with in vitro data obtained from pleural cells showing catumaxomab-induced proliferation of T cells and accessory cells and TH1-directed cytokine secretion. The data are equivalent to results observed in the peritoneal fluid of ascites patients. [Table: see text]
Databáze: OpenAIRE
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