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Rapid induction of apoptosis in B‐cell lymphoma by functionally isolated human antibodies
Author(s) -
Fransson Johan,
Tornberg UllaCarin,
Borrebaeck Carl A.K.,
Carlsson Roland,
Frendéus Björn
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21829
Subject(s) - antibody , lymphoma , biology , microbiology and biotechnology , apoptosis , antigen , receptor , recombinant dna , cell culture , b cell , b cell lymphoma , monoclonal antibody , cancer research , immunology , biochemistry , gene , genetics
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 μ 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 naïve phage libraries. © 2006 Wiley‐Liss, Inc.