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Target cell-induced t-cell activation with bispecific and trispecific antibody fragments

Academic Article
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Overview

authors

  • Jung, G.
  • Freimann, U.
  • Vonmarschall, Z.
  • Reisfeld, Ralph
  • Wilmanns, W.

publication date

  • October 1991

journal

  • European Journal of Immunology  Journal

abstract

  • Previously we proposed a concept for tumor immunotherapy in which two different bispecific antibody conjugates, an anti-target x anti-CD3 and an anti-target x anti-CD28 conjugate, induce the activation of resting human T cells upon binding to the respective tumor target cells. After in vivo application of these reagents, this model of a "target cell-induced T cell activation" envisages the destruction of target cells by in situ activated T cells. Obviously however, for in vivo application, the use of Fc-free antibody fragments is mandatory to prevent binding of the conjugates to Fc receptor-positive cells which would lead to Fc-mediated T cell activation. Here we report a simplification of published procedures for the generation of bispecific Fab-hybrid fragments, univalent for each antigen. We demonstrate that an anti-target x anti-CD3/anti-target x anti-CD28 combination of such hybrids, as well as an identical combination of covalently coupled F(ab')2 fragments, mediate "target cell-induced T cell activation" in an in vitro test system. Thus, these reagents may be capable of inducing an in situ activation of human T cells upon systemic in vivo application according to the concept outlined above. A trispecific conjugate with anti-target, anti-CD3- and anti-CD28 specificity appears to be unsuitable for this purpose because it activates resting T cells in soluble form without requiring immobilization through binding via its anti-target portion.

subject areas

  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Antigens, CD
  • Antigens, CD28
  • Antigens, CD3
  • Antigens, Differentiation, T-Lymphocyte
  • Humans
  • Immunoglobulin Fab Fragments
  • In Vitro Techniques
  • Lymphocyte Activation
  • Melanoma
  • Muromonab-CD3
  • Receptors, Antigen, T-Cell
  • Structure-Activity Relationship
  • T-Lymphocytes
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Identity

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/eji.1830211020

PubMed ID

  • 1655465
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Additional Document Info

start page

  • 2431

end page

  • 2435

volume

  • 21

issue

  • 10

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