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

Academic Article
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Overview

authors

  • Moller, S. A.
  • Reisfeld, Ralph

publication date

  • June 1991

journal

  • Cancer Immunology Immunotherapy  Journal

abstract

  • 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 x KS1/4 and OKT3 x KS1/4 to direct peripheral blood mononuclear cells (PBMC) specifically against OVCAR-3 ovarian carcinoma target cells was measured in a 4-h 51Cr-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 10-10,000 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.

subject areas

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, CD28
  • Antigens, CD3
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • Carcinoma
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Hybridomas
  • Interleukin-2
  • Lymphocyte Activation
  • Ovarian Neoplasms
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes
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Research

keywords

  • LYMPHOCYTES-T
  • MONOCLONAL ANTIBODY
  • OVARIAN CARCINOMA
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Identity

International Standard Serial Number (ISSN)

  • 0340-7004

Digital Object Identifier (DOI)

  • 10.1007/bf01744939

PubMed ID

  • 1647871
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Additional Document Info

start page

  • 210

end page

  • 216

volume

  • 33

issue

  • 4

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