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Modulation of the CD40-CD40 ligand interaction using human anti-CD40 single-chain antibody fragments obtained from the n-CoDeR phage display library

Ellmark, Peter LU ; Ottosson, Camilla; Borrebaeck, Carl LU ; Malmborg Hager, Ann-Christin LU and Furebring, Christina LU (2002) In Immunology 106(4). p.456-463
Abstract
CD40 plays a central regulatory role in the immune system and antibodies able to modulate CD40 signalling may consequently have a potential in immunotherapy, in particular for treatment of lymphomas and autoimmune disease like multiple sclerosis. As a first step to achieve this goal, we describe the selection and characterization of a novel set of fully human anti-CD40 antibody fragments (scFv) from a phage display library (n-CoDeR). In order to determine their biological potential, these antibody fragments have been analysed for their ability to promote B-cell activation, rescue from apoptosis and to block the CD40-CD40 ligand (CD40L) interaction. The selected cohort of human scFv could be subcategorized, each expressing a distinct... (More)
CD40 plays a central regulatory role in the immune system and antibodies able to modulate CD40 signalling may consequently have a potential in immunotherapy, in particular for treatment of lymphomas and autoimmune disease like multiple sclerosis. As a first step to achieve this goal, we describe the selection and characterization of a novel set of fully human anti-CD40 antibody fragments (scFv) from a phage display library (n-CoDeR). In order to determine their biological potential, these antibody fragments have been analysed for their ability to promote B-cell activation, rescue from apoptosis and to block the CD40-CD40 ligand (CD40L) interaction. The selected cohort of human scFv could be subcategorized, each expressing a distinct functional signature. Thus scFv were generated that induced B-cell proliferation, rescued B cells from apoptosis and blocked the CD40-CD40L interaction to different extents. In particular, one of the scFv clones (F33) had the ability to abrogate completely this interaction. The epitope recognition patterns as well as individual rate constants were also determined and the affinity was shown to vary from low to high nanomolar range. In conclusion, this panel of human anti-CD40 scFv fragments displays a number of distinct properties, which may constitute a valuable source when evaluating candidates for in vivo trials. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
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in
Immunology
volume
106
issue
4
pages
456 - 463
publisher
Wiley-Blackwell
external identifiers
  • wos:000177195600003
  • pmid:12153507
  • scopus:0036039462
ISSN
0019-2805
language
English
LU publication?
yes
id
c58957be-5df1-4efc-b433-f02e50dc2d3f (old id 109710)
alternative location
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12153507
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12153507&dopt=Abstract
date added to LUP
2007-06-28 09:43:52
date last changed
2017-01-01 04:55:42
@article{c58957be-5df1-4efc-b433-f02e50dc2d3f,
  abstract     = {CD40 plays a central regulatory role in the immune system and antibodies able to modulate CD40 signalling may consequently have a potential in immunotherapy, in particular for treatment of lymphomas and autoimmune disease like multiple sclerosis. As a first step to achieve this goal, we describe the selection and characterization of a novel set of fully human anti-CD40 antibody fragments (scFv) from a phage display library (n-CoDeR). In order to determine their biological potential, these antibody fragments have been analysed for their ability to promote B-cell activation, rescue from apoptosis and to block the CD40-CD40 ligand (CD40L) interaction. The selected cohort of human scFv could be subcategorized, each expressing a distinct functional signature. Thus scFv were generated that induced B-cell proliferation, rescued B cells from apoptosis and blocked the CD40-CD40L interaction to different extents. In particular, one of the scFv clones (F33) had the ability to abrogate completely this interaction. The epitope recognition patterns as well as individual rate constants were also determined and the affinity was shown to vary from low to high nanomolar range. In conclusion, this panel of human anti-CD40 scFv fragments displays a number of distinct properties, which may constitute a valuable source when evaluating candidates for in vivo trials.},
  author       = {Ellmark, Peter and Ottosson, Camilla and Borrebaeck, Carl and Malmborg Hager, Ann-Christin and Furebring, Christina},
  issn         = {0019-2805},
  language     = {eng},
  number       = {4},
  pages        = {456--463},
  publisher    = {Wiley-Blackwell},
  series       = {Immunology},
  title        = {Modulation of the CD40-CD40 ligand interaction using human anti-CD40 single-chain antibody fragments obtained from the n-CoDeR phage display library},
  volume       = {106},
  year         = {2002},
}