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

Fransson, Johan LU ; Tornberg, UC ; Borrebaeck, Carl LU ; Carlsson, Roland LU and Frendeus, B (2006) In International Journal of Cancer 119(2). p.349-358
Abstract
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... (More)
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. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
intercellular, apoptosis, antibody library, phage display, B lymphoma, adhesion molecule-1
in
International Journal of Cancer
volume
119
issue
2
pages
349 - 358
publisher
John Wiley and Sons
external identifiers
  • wos:000238267300014
  • pmid:16477633
  • scopus:33745220111
ISSN
0020-7136
DOI
10.1002/ijc.21829
language
English
LU publication?
yes
id
0a41254e-efcf-4e97-bad1-f3950d689454 (old id 406062)
date added to LUP
2016-04-01 12:31:51
date last changed
2021-09-22 02:59:37
@article{0a41254e-efcf-4e97-bad1-f3950d689454,
  abstract     = {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.},
  author       = {Fransson, Johan and Tornberg, UC and Borrebaeck, Carl and Carlsson, Roland and Frendeus, B},
  issn         = {0020-7136},
  language     = {eng},
  number       = {2},
  pages        = {349--358},
  publisher    = {John Wiley and Sons},
  series       = {International Journal of Cancer},
  title        = {Rapid induction of apoptosis in B-cell lymphoma by functionally isolated human antibodies},
  url          = {http://dx.doi.org/10.1002/ijc.21829},
  doi          = {10.1002/ijc.21829},
  volume       = {119},
  year         = {2006},
}