The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties

European Journal of Immunology
S BoltH Waldmann


CD3 antibodies are proven immunosuppressants capable of reversing transplant rejection episodes. Their general application has been limited both by their immunogenicity and, in particular, by the "first-dose" cytokine-release syndrome experienced by patients after the initial administration of antibody. We have produced a set of variants of the humanized YTH 12.5 CD3 monoclonal antibody (mAb) (Routledge et al., Eur. J. Immunol. 1991. 21: 2717) bearing different human heavy (H) chain constant regions, with the intention of finding a form of the antibody that is not able to activate T cells. Comparison of the variants having gamma 1, gamma 2, gamma 3 and gamma 4 H chains in a competitive binding assay showed that antibody avidity was not affected by IgG subclass. Using a sensitive indicator of FcR binding activity (the capacity of the CD3 mAb to redirect cytotoxic T cells to kill the monocytic cell line U-937) we demonstrated a functional hierarchy of gamma 1 = gamma 4 > alpha 2 =/> gamma 3 mb > gamma 2. An aglycosyl version of the gamma 1 CD3 mAb, produced by site-directed mutagenesis (Asn297 to Ala), still had considerable activity in this assay (intermediate to the gamma 1 and alpha 2 CD3 mAb), albeit at a level approximately ...Continue Reading


Jan 1, 1991·The Journal of Experimental Medicine·A de la HeraA Tunnacliffe
Nov 1, 1991·European Journal of Immunology·E G RoutledgeH Waldmann
Dec 1, 1990·The Journal of Experimental Medicine·C AnasettiP J Martin
Aug 1, 1990·The Pediatric Infectious Disease Journal·M A French
Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·P GunningL Kedes
Apr 18, 1985·Nature·U D StaerzM J Bevan
Aug 8, 1985·The New England Journal of Medicine·Ortho Multicenter Transplant Study Group
Oct 28, 1988·Science·J D EllenhornJeffrey A Bluestone
Dec 1, 1985·European Journal of Immunology·U D Staerz, M J Bevan
Mar 24, 1988·Nature·L RiechmannG Winter
Dec 4, 1986·Nature·A M WeissmanR D Klausner
Dec 13, 1984·Nature·M S NeubergerR O Fox
Nov 1, 1982·European Journal of Immunology·L ChatenoudJ F Bach


Nov 26, 2002·Journal of Molecular Recognition : JMR·Paul A Ramsland, William Farrugia
Jun 21, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Samuel W Hall, Anne Cooke
Dec 1, 1992·Current Opinion in Biotechnology·H WaldmannJ Isaacs
Feb 1, 1997·Transplantation Proceedings·L Chatenoud
Nov 22, 1997·Current Opinion in Immunology·J A Smith, Jeffrey A Bluestone
Jun 2, 2011·Nature Reviews. Drug Discovery·Frank Waldron-Lynch, Kevan C Herold
Apr 20, 2006·Nature Reviews. Immunology·Paul J Carter
Jul 21, 2007·Nature Reviews. Immunology·Lucienne Chatenoud, Jeffrey A Bluestone
Jun 24, 2005·The New England Journal of Medicine·Bart KeymeulenLucienne Chatenoud
Mar 5, 2011·Molecular & Cellular Proteomics : MCP·Jun WangManfred Wuhrer
May 7, 2010·Hybridoma·Luis E HinojosaAlejandro López-Requena
Dec 28, 1999·Transplantation·R F Wood, A G Pockley
Dec 3, 2010·Current Opinion in Rheumatology·Ajay NirulaFrederick R Taylora
Sep 9, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Stephen P Cobbold
Feb 4, 2011·Science Translational Medicine·Damien Bresson, Matthias G von Herrath
Oct 13, 2006·Annual Review of Immunology·James N ArnoldRaymond A Dwek
Sep 22, 2006·Annual Review of Medicine·E William St ClairJeffrey A Bluestone
Sep 17, 2005·The Journal of Clinical Investigation·Brygida C BisikirskaKevan C Herold
May 17, 2013·The Journal of Clinical Investigation·Terry B Strom
Jan 1, 2012·The Review of Diabetic Studies : RDS·Lucienne Chatenoud, H Waldmann
Feb 14, 2013·The Review of Diabetic Studies : RDS·Benno WeigmannCarolin Daniel
Nov 3, 2010·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Etsuji Kaneko, Rinpei Niwa
Nov 8, 2011·Immunotherapy·Ben SprangersChantal Mathieu
Feb 10, 2010·International Journal of Diabetes in Developing Countries·C B Sanjeevi
Dec 14, 2011·Clinical & Developmental Immunology·Andre Pires da Cunha, Howard L Weiner
Sep 1, 1994·Transplant Immunology·S MasroorM R First
Jan 26, 2010·Expert Opinion on Biological Therapy·Umesh B Masharani, Joseph Becker
Jun 7, 2005·Expert Opinion on Biological Therapy·Takanori Kanai, Mamoru Watanabe
Aug 28, 2015·Clinical and Experimental Immunology·S I ManneringT W H Kay
Nov 10, 2009·Current Opinion in Biotechnology·William R Strohl
Sep 23, 2008·Journal of the Neurological Sciences·Hirofumi OchiHoward L Weiner
Jun 26, 2008·Current Opinion in Immunology·Aran F LabrijnJanine Schuurman
Nov 3, 2007·Advanced Drug Delivery Reviews·Ping-Ying PanShu-Hsia Chen
Feb 9, 2005·Annals of the New York Academy of Sciences·Brygida C Bisikirska, Kevan C Herold
Aug 30, 2005·Annals of the New York Academy of Sciences·Naru BabayaGeorge S Eisenbarth
Mar 26, 2009·Diabetes/metabolism Research and Reviews·Adam Kaufman, Kevan C Herold
Sep 11, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S R DaleyH Waldmann
Mar 13, 2012·Journal of Molecular Recognition : JMR·Thomas C NessporRandall J Brezski
Feb 24, 2010·Arthritis and Rheumatism·Hans U SchererRené E M Toes
Sep 11, 2010·Current Opinion in Immunology·Adrian R Kendal, H Waldmann
Oct 3, 2006·Current Opinion in Immunology·Lucienne Chatenoud
Aug 15, 2006·Advanced Drug Delivery Reviews·Leonard G Presta
May 25, 2006·Human Immunology·P van de LindeB O Roep
Oct 11, 2005·Current Opinion in Immunology·Lucienne Chatenoud
Jul 3, 2002·Endocrinology and Metabolism Clinics of North America·Lucienne Chatenoud
Jul 5, 2006·International Reviews of Immunology·Lucienne Chatenoud
Sep 14, 2001·Best Practice & Research. Clinical Endocrinology & Metabolism·F K GorusBelgian Diabetes Registry
May 11, 2016·Immunotherapy·Chantal Kuhn, Howard L Weiner
Feb 4, 2011·Science Translational Medicine·Chantal KuhnLucienne Chatenoud
Jan 7, 2017·Journal of Pharmaceutical Sciences·M Jack BorrokP Tsui
May 19, 2010·Expert Review of Clinical Immunology·Peter J BugelskiEsther Bouman-Thio
Jul 1, 2009·Therapeutic Advances in Neurological Disorders·Claire L Helliwell, Alasdair J Coles
Dec 12, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amelia K HajDavid H O'Connor
Oct 1, 1995·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·F Shakib
Jun 27, 2006·Journal of Immunotherapy·Bernard J ScallonMarian T Nakada
Jun 1, 1996·European Journal of Immunology·J GroeninkM F van den Broek
Mar 1, 1996·European Journal of Immunology·J Girdlestone, M Wing
Jul 1, 1997·European Journal of Immunology·R ScullyH Waldmann
Jul 18, 2009·Current Opinion in Organ Transplantation·Lucienne Chatenoud
Feb 23, 2010·Nature Reviews. Endocrinology·Lucienne Chatenoud
Apr 24, 2010·Nature Reviews. Immunology·Andrew C Chan, Paul J Carter
Feb 4, 2003·Nature Reviews. Immunology·Lucienne Chatenoud
Jan 21, 2011·Physiological Reviews·Tom L van BelleMatthias G von Herrath
Dec 11, 2019·Antibodies·Mark L ChiuGary L Gilliland
Feb 23, 2019·Scientific Reports·Maria José CostaShu-Hui Liu
Sep 22, 2001·The Journal of Biological Chemistry·Y MimuraR Jefferis
May 26, 2001·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·H WaldmannS Cobbold
Sep 29, 2005·Expert Opinion on Biological Therapy·Lucienne Chatenoud, Jean-François Bach
Sep 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dawn Winsor-HinesPaul D Ponath
Feb 4, 2016·World Journal of Hepatology·Mustafa S AschaIbrahim A Hanouneh
Oct 8, 2017·Protein & Cell·Xinhua WangRandall J Brezski
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M P ReddyA Truneh
Feb 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Li ZuoRaphael Hirsch
Feb 13, 2007·Médecine sciences : M/S·Lucienne Chatenoud
Aug 20, 2017·Protein & Cell·William R Strohl
Nov 21, 1997·Clinical and Experimental Immunology·J D IsaacsH Waldmann
Jan 5, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthias G von HerrathLucienne Chatenoud
Apr 24, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Algirdas GrevysJan Terje Andersen
Jan 31, 2018·Frontiers in Immunology·Juan C AlmagroManuel L Penichet
Aug 22, 2003·Clinical and Experimental Immunology·L Renders, T Valerius
Nov 15, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maximilian BrinkhausGestur Vidarsson
Dec 30, 2014·Cancer Immunology Research·Hong XuNai-Kong V Cheung

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