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Rapid induction of apoptosis in B-cell lymphoma by functionally isolated human antibodies

Author:
  • Johan Fransson
  • UC Tornberg
  • Carl Borrebaeck
  • Roland Carlsson
  • B Frendeus
Publishing year: 2006
Language: English
Pages: 349-358
Publication/Series: International Journal of Cancer
Volume: 119
Issue: 2
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

Novel panning and screening methodology was devised to isolate high affinity human recombinant scFv antibody fragments with functionally associated properties in B lymphoma cells. The approach was used to generate a panel of apoptosis-inducing antibodies specific for antigens differentially expressed in B lymphoma vs. T leukaemia cells. The selections resulted in an antibody pool with near perfect selectivity (> 99%) for the B lymphoma target cells. Randomly picked clones (72) revealed 7 unique antibody genotypes. Six of these rapidly induced apoptosis in target cells. Following the conversion to full IgGs, the antibodies were shown to be specific for HLA-DR/DP, the B-cell receptor p chain and for CD54/ICAM-1. The latter receptor was not previously associated with apoptotic properties in B-cell lymphomas. Anti-ICAM-1 IgG induced apoptosis in a broad range of B lymphoma cell lines and were shown by immunohistochemistry to bind strongly to B lymphoma tissue obtained from 5 different B lymphoma patients. The recombinant IgG antibodies had affinities in the subnanomolar (0.3 nM) to nanomolar (3 nM) range. The described technology is generally applicable for the rapid isolation of high affinity human antibodies with specificity for differentially expressed cell surface receptors with intrinsic negative or positive signalling properties from naive phage libraries. (c) 2006 Wiley-Liss, Inc.

Keywords

  • Cancer and Oncology
  • intercellular
  • apoptosis
  • antibody library
  • phage display
  • B lymphoma
  • adhesion molecule-1

Other

Published
  • ISSN: 0020-7136
Carl Borrebaeck
E-mail: carl [dot] borrebaeck [at] immun [dot] lth [dot] se

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Department of Immunotechnology

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