Carl Borrebaeck
Professor
Rapid induction of apoptosis in B-cell lymphoma by functionally isolated human antibodies
Author
Summary, in 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.
Department/s
- Department of Immunotechnology
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 Inc.
Topic
- Cancer and Oncology
Keywords
- intercellular
- apoptosis
- antibody library
- phage display
- B lymphoma
- adhesion molecule-1
Status
Published
ISBN/ISSN/Other
- ISSN: 0020-7136