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Efficient carcinoma cell killing by activated polymorphonuclear neutrophils targeted with an Ep-CAM×CD64 (HEA125×197) bispecific antibody

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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, HEA125×197, 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-γ)-stimulated polymorphonuclear neutrophils to induce CD64 expression, bsAb HEA125×197 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×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 HEA125×197 may broaden the spectrum of bispecific reagents for the treatment of epithelial malignancies.

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Authors and Affiliations

  1. Department of Molecular Immunology (G0400), German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, , , , ,

    Christof Schweizer & Gerhard Moldenhauer

  2. Department of Obstetrics and Gynecology, University of Heidelberg, Children's Hospital, University of Ulm, Ulm, Germany, , , , ,

    Gudrun Strauss

  3. Heidelberg, Germany, , , , ,

    Matthias Lindner & Alexander Marmé

  4. Medarex Inc., Annandale, NJ, USA, , , , ,

    Yashwant M. Deo

Authors
  1. Christof Schweizer
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  2. Gudrun Strauss
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  3. Matthias Lindner
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  4. Alexander Marmé
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  5. Yashwant M. Deo
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  6. Gerhard Moldenhauer
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Schweizer, C., Strauss, G., Lindner, M. et al. Efficient carcinoma cell killing by activated polymorphonuclear neutrophils targeted with an Ep-CAM×CD64 (HEA125×197) bispecific antibody. Cancer Immunol Immunother 51, 621–629 (2002). https://doi.org/10.1007/s00262-002-0326-y

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  • DOI: https://doi.org/10.1007/s00262-002-0326-y