Opsonization with a trifunctional bispecific (αCD3 x αEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes

  • Authors:
    • M. Schmitt
    • A. Schmitt
    • P. Reinhardt
    • B. Thess
    • B. Manfras
    • H. Lindhofer
    • H. Riechelmann
    • M. Wiesneth
    • S. Gronau
  • View Affiliations

  • Published online on: October 1, 2004     https://doi.org/10.3892/ijo.25.4.841
  • Pages: 841-848
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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 γ, and c) granzyme B mediated lysis of targeted BHY cells by EpCAM specific CD8+ T cells. The secretion of tumor necrosis factor α, interferon γ and interleukin-2 by opsonized PBMN was significantly reduced after 24 h. Washed opsonized PBMN maintained their lytic activity against tumor cells as tested on the CAM. Removab is an appropriate agent for the therapeutic amplification of T cell responses against EpCAM+ tumor cells by opsonization of PBMN without putting patients at risk for severe adverse events caused by a cytokine storm.

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October 2004
Volume 25 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Schmitt, M., Schmitt, A., Reinhardt, P., Thess, B., Manfras, B., Lindhofer, H. ... Gronau, S. (2004). Opsonization with a trifunctional bispecific (αCD3 x αEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes. International Journal of Oncology, 25, 841-848. https://doi.org/10.3892/ijo.25.4.841
MLA
Schmitt, M., Schmitt, A., Reinhardt, P., Thess, B., Manfras, B., Lindhofer, H., Riechelmann, H., Wiesneth, M., Gronau, S."Opsonization with a trifunctional bispecific (αCD3 x αEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes". International Journal of Oncology 25.4 (2004): 841-848.
Chicago
Schmitt, M., Schmitt, A., Reinhardt, P., Thess, B., Manfras, B., Lindhofer, H., Riechelmann, H., Wiesneth, M., Gronau, S."Opsonization with a trifunctional bispecific (αCD3 x αEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes". International Journal of Oncology 25, no. 4 (2004): 841-848. https://doi.org/10.3892/ijo.25.4.841