Treatment of murine B cell lymphoma with bispecific monoclonal antibodies (anti-idiotype x anti-CD3)

J Immunol. 1991 Aug 1;147(3):1091-7.

Abstract

It has previously been reported that T lymphocytes can be targeted by using bispecific antibodies consisting of anti-target antibody and anti-CD3. In the present study, a bispecific mAb was developed by somatic hybridization of mouse hybridomas, one producing a mAb against the Id determinant of the mouse B cell lymphoma 38C13 and the other a mAb against a polymorphic determinant on murine CD3. The bispecific antibody, anti-38C13 x anti-CD3, is bi-isotypic (IgG1 x IgG2a) and was purified by ion exchange and affinity chromatography. The dual specificity of the hybrid hybridoma-produced mAb could be demonstrated by flow cytometry, the induction of T cell proliferation, the induction of IL-2 secretion by polyclonal T cells, and redirected lysis of the relevant target cells. The hybrid (bi-isotypic) Fc part of the bispecific antibodies was nonfunctional in FcR-dependent redirected lysis. In vivo studies demonstrate that this bispecific mAb could efficiently target T cells towards the tumor cells, resulting in long term survival and cure of the lymphoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD3 Complex
  • Cell Division / immunology
  • Chromatography, Ion Exchange
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Immunoglobulin G / immunology*
  • Immunotherapy*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation / immunology
  • Lymphoma, B-Cell / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Immunoglobulin G
  • Interleukin-2
  • Receptors, Antigen, T-Cell