PMID: 9171898Dec 1, 1996Paper

Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv

Molecular Immunology
T C ThomasM J Evans

Abstract

Activation of the complement system contributes significantly to the pathogenesis of numerous acute and chronic diseases. Recently, a monoclonal antibody (5G1.1) that recognizes the human complement protein C5, has been shown to effectively block C5 cleavage, thereby preventing the generation of the pro-inflammatory complement components C5a and C5b-9. Humanized 5G1.1 antibody, Fab and scFv molecules have been produced by grafting the complementarity determining regions of 5G1.1 on to human framework regions. Competitive ELISA analysis indicated that no framework changes were required in the humanized variable regions for retention of high affinity binding to C5, even at framework positions predicted by computer modeling to influence CDR canonical structure. The humanized Fab and scFv molecules blocked complement-mediated lysis of chicken erythrocytes and porcine aortic endothelial cells in a dose-dependent fashion, with complete complement inhibition occurring at a three-fold molar excess, relative to the human C5 concentration. In contrast to a previously characterized anti-C5 scFv molecule, the humanized h5G1.1 scFv also effectively blocked C5a generation. Finally, an intact humanized h5G1.1 antibody blocked human complement...Continue Reading

Associated Clinical Trials

References

Aug 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·J G SeidmanP Leder
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P CarterH M Shepard
Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·H M JäckM Wabl
Mar 20, 1992·Journal of Molecular Biology·J Foote, G Winter
Sep 1, 1991·Immunology Today·P J Lachmann
Jan 24, 1991·Nature·G Winter, C Milstein
Jul 18, 1990·Journal of the National Cancer Institute·D ColcherJ Schlom
Jul 1, 1990·Clinical and Experimental Immunology·F HugoS Bhakdi
Dec 21, 1989·Nature·C ChothiaW R Tulip
Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A F LoBuglioM B Khazaeli
Mar 24, 1988·Nature·L RiechmannG Winter
Aug 20, 1987·Journal of Molecular Biology·C Chothia, A M Lesk
Feb 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·G RechaviD Givol
Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·Y WangL A Matis
Nov 3, 1994·The New England Journal of Medicine·T Höhler, K H Büschenfelde
Apr 1, 1994·European Journal of Clinical Investigation·B P Morgan
Jan 1, 1994·Journal of Immunotherapy with Emphasis on Tumor Immunology : Official Journal of the Society for Biological Therapy·M B KhazaeliA F LoBuglio
Jun 23, 1994·The New England Journal of Medicine·D B Drachman
Jun 30, 1994·The New England Journal of Medicine·J A Mills
Dec 1, 1993·European Journal of Immunology·R KleinH G Zachau
Dec 1, 1993·European Journal of Immunology·R Klein, H G Zachau
Mar 1, 1993·The Annals of Thoracic Surgery·A M GillinovA Herskowitz
Mar 1, 1996·European Journal of Immunology·V GhetieE S Ward
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·R P Junghans, C L Anderson
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y WangL A Matis

❮ Previous
Next ❯

Citations

Jul 4, 2012·Journal of Neurology·Joerg-Patrick Stübgen
Dec 10, 2013·International Journal of Hematology·Suresh K KrishnanRichard J Kelly
Dec 5, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Sabeen Lulu, Emmanuelle Waubant
Sep 11, 2002·Molecular Immunology·Jörg AndräDieter Paul
Aug 14, 2003·Molecular Immunology·Tom E Mollnes, Arnt E Fiane
Sep 12, 2002·Trends in Molecular Medicine·Richard J Quigg
Feb 14, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Sherry D FlemingGeorge C Tsokos
Mar 9, 2011·Molecular Pharmaceutics·Luis J CruzCarl G Figdor
May 11, 2013·Cancer Gene Therapy·D MaggeD L Bartlett
Oct 13, 2006·Nature Biotechnology·Yi Wang
Nov 9, 2007·Nature Biotechnology·Daniel Ricklin, John D Lambris
Aug 24, 2007·Nature Reviews. Drug Discovery·Charles J ParkerPeter Kirkpatrick
Jan 30, 2008·Immunology and Cell Biology·Hyun LeeCharles R Mackay
Mar 21, 2002·Fundamental & Clinical Pharmacology·T MonsinjonM Fontaine
Nov 25, 2003·Kidney International·Richard J Quigg
Dec 11, 2002·Kidney International·Thiruma V ArumugamStephen M Taylor
Feb 6, 2004·The New England Journal of Medicine·Peter HillmenRussell P Rother
Sep 23, 2006·The New England Journal of Medicine·Peter HillmenLucio Luzzatto
Feb 24, 2005·Current Opinion in Hematology·Karina Yazdanbakhsh
Jan 28, 2005·Journal of Cardiac Surgery·John C ChenUNKNOWN Pexelizumab Study Investigators
Dec 1, 2012·Case Reports in Nephrology and Urology·Patricia Hirt-MinkowskiJürg A Schifferli
Jul 17, 2012·Anesthesia and Analgesia·Gregory L StahlJerrold H Levy
Aug 24, 2006·International Journal of Hematology·Lucio Luzzatto, Giacomo Gianfaldoni
Jun 9, 2012·Journal of the American Society of Nephrology : JASN·Leal C HerlitzVivette D D'Agati
Aug 27, 2009·Biologics : Targets & Therapy·Prathit A Kulkarni, Vahid Afshar-Kharghan
Dec 17, 2009·Therapeutics and Clinical Risk Management·Richard KellyAnita Hill
Jan 20, 2004·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Anil Nigam, Stephen L Kopecky
Jun 27, 2009·Clinical Journal of the American Society of Nephrology : CJASN·Christoph J MacheEkkehard Ring
Nov 19, 2010·Bioanalysis·Bing KuangHuifen Faye Wang
Jan 22, 2003·Xenotransplantation·F CicchettiO Isacson
Jul 30, 2014·Future Medicinal Chemistry·David C Swinney, Shuangluo Xia
Jul 5, 2005·Expert Opinion on Investigational Drugs·M K Liszewski, J P Atkinson
Feb 22, 2016·International Journal of Cardiology·Tom J O'DonohoeNatkunam Ketheesan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.