PMID: 15375531Sep 18, 2004Paper

Opsonization with a trifunctional bispecific (alphaCD3 x alphaEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes

International Journal of Oncology
M SchmittS Gronau

Abstract

Removab is a trifunctional bispecific antibody which can bridge CD3+ T cells and epithelial cell adhesion molecule positive (EpCAM+) tumor cells, and binds with its Fc fragment to antigen presenting cells. To explore a new approach for the treatment of patients with carcinoma of the upper aerodigestive tract, we investigated whether Removab can induce specific cellular responses to the EpCAM+ carcinoma cell line BHY. Particular emphasis was put on the opsonization of peripheral blood mononuclear cells (PBMN) with respect to clinical application. Tumor cells and allogeneic PBMN of healthy volunteers were incubated with or without Removab. In a third group, PBMN were opsonized with Removab and washed before incubation with tumor cells. Inverse microscopy, ELISPOT, flow cytometry analysis and cytotoxicity assays on the chorioallantois membrane (CAM) were performed. In comparison with PBMN alone, opsonization with Removab resulted in: a) activation of CD83+ antigen presenting cells, b) secretion of interferon gamma, and c) granzyme B mediated lysis of targeted BHY cells by EpCAM specific CD8+ T cells. The secretion of tumor necrosis factor alpha, interferon gamma and interleukin-2 by opsonized PBMN was significantly reduced after 2...Continue Reading

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