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

Författare:
Publiceringsår: 2006
Språk: Engelska
Sidor: 349-358
Publikation/Tidskrift/Serie: International Journal of Cancer
Volym: 119
Nummer: 2
Dokumenttyp: Artikel
Förlag: Wiley-Liss

Sammanfattning

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.

Disputation

Nyckelord

  • Medicine and Health Sciences
  • Technology and Engineering
  • intercellular
  • apoptosis
  • antibody library
  • phage display
  • B lymphoma
  • adhesion molecule-1

Övriga

Published
Yes
  • ISSN: 0020-7136

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