Artikel
Intratumoral application of trispecific antibody in patients with SCCHN
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Veröffentlicht: | 22. September 2005 |
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Gliederung
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The tri-functional monoclonal antibody removab® (BIU III) represents a new concept of immuntherapeutic treatment for EpCAM-overexpressing epithelial tumors. BIU III is an intact bispecific monoclonal antibody with specificities against EpCAM and CD3. In addition, it binds to Fc-receptors of distinct blood cells and is therefore called „tri-functional“ antibody. Its principle was shown to result in efficient eradication of tumor cells by accessory cell-induced phagocytosis, T-cell mediated lysis and apoptosis.
Four patients with SCCHN were treated with BIU III and received 2 or 3 intratumoral applications of removab at intervals of 3 days. The vital signs were frequently monitored during and for 24 h after the administration of the BIU III. Serial blood samples were drawn from patients before, immediately after and 4, 12, and 24h after intratumoral application of BIU III. Concentrations of circulating lymphocyte subsets and interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-18, GM-CSF, IFN- and TNF- were determined using enzyme-linked immunosorbent assay and flow cytometric analysis. All patients tolerated the treatment generally well, without reaching dose-limiting toxicity, liver enzymes were reversibly induced due the cytokine release syndome.
The immunological parameters have shown a massive increase in immunorelevant cytokines IL6/TNF- leading to an activated immune system e.g. IL-2, equally a significant increase of CD4/CD8 T-cells and activated cells CD4/CD25 and CD8/HLA-DR in peripheral blood.
Supported by: Fresenius Haemocare; Klara-Kreitz-Stiftung