PMID- 9079800
OWN - NLM
STAT- MEDLINE
DCOM- 19970429
LR  - 20061115
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 27
IP  - 3
DP  - 1997 Mar
TI  - Dimerization of Fab fragments enables ready screening of phage antibodies that 
      affect hepatocyte growth factor/scatter factor activity on target cells.
PG  - 618-23
AB  - A number of applications of antibodies in diagnosis and therapy require 
      multivalent reagents either because of the polymeric nature of the antigens or 
      because biological activity depends on an effect on the formation of homodimeric 
      species. Here, we report a procedure for mass screening of phage-derived 
      monomeric antibody fragments that depend on valency for activity. As a model 
      system, a set of 13 phage-derived human Fab fragments were first selected against 
      mouse and human recombinant hepatocyte growth factor/scatter factor (HGF/SF), a 
      high molecular weight polypeptide growth factor related to the blood protease 
      plasminogen and involved in development and cancer. These Fab fragments were 
      subsequently screened for an effect on HGF/SF activity either as monomeric 
      fragments or after dimerization with a monoclonal antibody (9E10) directed 
      against a peptide tag on the fragments. Fab were identified that either inhibited 
      or enhanced HGF/SF activity on target cell lines, but dimerization was required 
      for this effect. The approach proposed should facilitate mass screening of 
      phage-derived antibody fragments that depend on multiple valency for activity.
FAU - Zaccolo, M
AU  - Zaccolo M
AD  - Imperial Cancer Research Fund Laboratory, MRC Centre, Cambridge, GB. 
      m_zaccolo@europa.lif.icnet.uk
FAU - Griffiths, A P
AU  - Griffiths AP
FAU - Prospero, T D
AU  - Prospero TD
FAU - Winter, G
AU  - Winter G
FAU - Gherardi, E
AU  - Gherardi E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Immunoglobulin kappa-Chains)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Recombinant Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Coliphages
MH  - Hepatocyte Growth Factor/*immunology
MH  - Humans
MH  - Immunoglobulin Fab Fragments/*chemistry/immunology
MH  - Immunoglobulin Heavy Chains/chemistry
MH  - Immunoglobulin kappa-Chains/chemistry
MH  - Macromolecular Substances
MH  - Methods
MH  - Mice
MH  - Protein Binding
MH  - Recombinant Proteins
MH  - Structure-Activity Relationship
EDAT- 1997/03/01 00:00
MHDA- 1997/03/01 00:01
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 1997/03/01 00:01 [medline]
PHST- 1997/03/01 00:00 [entrez]
AID - 10.1002/eji.1830270307 [doi]
PST - ppublish
SO  - Eur J Immunol. 1997 Mar;27(3):618-23. doi: 10.1002/eji.1830270307.