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Bispecific-monoclonal-antibody-directed lysis of ovarian carcinoma cells by activated human T lymphocytes

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Summary

Two different bispecific hybrid antibodies were established by fusing a hybridoma producing monoclonal antibody (mAb) against the pancarcinoma antigen KS1/4 with either of the two hybridomas OKT3 and 9.3, secreting antibodies reactive with the T cell determinants CD3 and CD28, respectively. The KS1/4 antibody reacts with a 40-kDa cell-surface glycoprotein antigen that is expressed on the surface of a variety of adenocarcinoma cells, including ovarian carcinoma. The ability of the bispecific antibodies 9.3⋅KS1/4 and OKT3⋅KS1/4 to direct peripheral blood mononuclear cells (PBMC) specifically against OVCAR-3 ovarian carcinoma target cells was measured in a 4-h51Cr-release assay. The bispecific antibodies were four to six times more potent in killing the OVCAR-3 target cells when compared to their parental antibodies either alone or in combination. A dose-dependent response was observed in the 10–10000 ng/ml range. The specificity of the targeting was demonstrated by the complete inhibition of cytotoxic activity following pre-incubation of tumor target cells with the parental mAb and by the lack of killing of KS1/4-negative target cell lines. An evaluation of the efficacy of PBMC from ovarian cancer patients as effector cells revealed that their specific cytotoxicity against OVCAR-3 cells was enhanced severalfold by bispecific antibodies as compared to parental antibodies. Furthermore, stimulation of PBMC with immobilized CD3 and interleukin-2 for 4 days resulted in an enhanced directed killing of human ovarian carcinoma cells by human T effector cells and the bispecific antibodies.

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Author notes

  1. Susanna A. Möller

    Present address: Dept. of Medical and Physiological Chemistry, Lund University, P. O. Box 94, S-221 00, Lund, Sweden

Authors and Affiliations

  1. Department of Immunology, Scripps Clinic and Research Foundation, 10666 North Torrey Pines road, 92037, La Jolla, CA, USA

    Susanna A. Möller & Ralph A. Reisfeld

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  1. Susanna A. Möller
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  2. Ralph A. Reisfeld
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Möller, S.A., Reisfeld, R.A. Bispecific-monoclonal-antibody-directed lysis of ovarian carcinoma cells by activated human T lymphocytes. Cancer Immunol Immunother 33, 210–216 (1991). https://doi.org/10.1007/BF01744939

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  • DOI: https://doi.org/10.1007/BF01744939

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