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Efficient carcinoma cell killing by activated polymorphonuclear neutrophils targeted with an Ep-CAMxCD64 (HEA125x197) bispecific antibody.

Abstract
Bispecific antibodies (bsAb) have attracted much attention over the past several years as a mean to improve immunotherapy of cancer. Due to their dual specificity, bsAb are able to redirect effector cells against tumor targets. In this study, the development and preclinical testing of a new quadroma-derived bsAb, HEA125x197, recognizing the tumor-associated Ep-CAM antigen and the high affinity Fc receptor for IgG, CD64, is reported. Using granulocyte-colony stimulating factor (G-CSF) and interferon-gamma (IFN-gamma)-stimulated polymorphonuclear neutrophils to induce CD64 expression, bsAb HEA125 x 197 elicited strong cytotoxic activity towards allogeneic and autologous ovarian carcinoma cells. The cytolytic efficiency of this antibody was comparable to that of a previously described bsAb, HEA125 x OKT3, targeting preactivated T lymphocytes against Ep-CAM-carrying tumor cells. Based on the pan-carcinoma specificity and the stable expression of Ep-CAM, bsAb HEA125x197 may broaden the spectrum of bispecific reagents for the treatment of epithelial malignancies.
AuthorsChristof Schweizer, Gudrun Strauss, Matthias Lindner, Alexander Marmé, Yashwant M Deo, Gerhard Moldenhauer
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 51 Issue 11-12 Pg. 621-9 (Dec 2002) ISSN: 0340-7004 [Print] Germany
PMID12439607 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Bispecific
  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Receptors, IgG
Topics
  • Adenocarcinoma (pathology, therapy)
  • Antibodies, Bispecific
  • Antigens, Neoplasm (immunology)
  • Cell Adhesion Molecules (immunology)
  • Cytotoxicity, Immunologic
  • Epithelial Cell Adhesion Molecule
  • Female
  • HL-60 Cells
  • Humans
  • Neutrophils (immunology)
  • Ovarian Neoplasms (pathology, therapy)
  • Receptors, IgG (immunology)
  • T-Lymphocytes (immunology)

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