Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus

The New England Journal of Medicine
Kevan C HeroldJeffrey A Bluestone

Abstract

Type 1 diabetes mellitus is a chronic autoimmune disease caused by the pathogenic action of T lymphocytes on insulin-producing beta cells. Previous clinical studies have shown that continuous immune suppression temporarily slows the loss of insulin production. Preclinical studies suggested that a monoclonal antibody against CD3 could reverse hyperglycemia at presentation and induce tolerance to recurrent disease. We studied the effects of a nonactivating humanized monoclonal antibody against CD3--hOKT3gamma1(Ala-Ala)--on the loss of insulin production in patients with type 1 diabetes mellitus. Within 6 weeks after diagnosis, 24 patients were randomly assigned to receive either a single 14-day course of treatment with the monoclonal antibody or no antibody and were studied during the first year of disease. Treatment with the monoclonal antibody maintained or improved insulin production after one year in 9 of the 12 patients in the treatment group, whereas only 2 of the 12 controls had a sustained response (P=0.01). The treatment effect on insulin responses lasted for at least 12 months after diagnosis. Glycosylated hemoglobin levels and insulin doses were also reduced in the monoclonal-antibody group. No severe side effects occu...Continue Reading

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Sep 26, 2015·Diabetes Care·Diane K WherrettType 1 Diabetes TrialNet Study Group
Feb 13, 2014·Liver International : Official Journal of the International Association for the Study of the Liver·Gabriel MarceauFernando Alvarez
Jan 13, 2015·Molecular Aspects of Medicine·Michael P MorranMassimo Pietropaolo
May 21, 2013·International Immunopharmacology·Tony L H ChuCaigan Du
Oct 8, 2009·Clinical Science·Michael D McCallA M James Shapiro
Jun 19, 2013·Journal of Autoimmunity·Tobias BoettlerMatthias G von Herrath
Jul 19, 2013·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Martijn J C Van HerwijnenFemke Broere
Mar 22, 2012·Autoimmunity·Eliana Mariño, Shane T Grey
Dec 2, 2005·International Reviews of Immunology·Wei ChenKevan C Herold
Dec 2, 2005·International Reviews of Immunology·Kevin S Goudy, Roland M Tisch
Dec 2, 2005·International Reviews of Immunology·Christophe M FilippiMatthias G von Herrath
Jul 5, 2006·International Reviews of Immunology·Lucienne Chatenoud
Jul 23, 2005·International Reviews of Immunology·Lucienne Chatenoud, Jean-François Bach
Jun 26, 2014·Expert Opinion on Pharmacotherapy·Albert J Czaja
Apr 15, 2016·Current Diabetes Reports·Connor J DwyerThomas R Malek
Jun 24, 2015·Current Opinion in Pharmacology·Lucienne Chatenoud
Mar 21, 2015·Archivum Immunologiae Et Therapiae Experimentalis·Y Maurice MorillonRoland M Tisch
Feb 3, 2004·The Journal of Clinical Investigation·Sefina ArifMark Peakman
Feb 6, 2003·The Journal of Clinical Investigation·Kevan C HeroldJeffrey A Bluestone
Aug 12, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Moufida Ben NasrPaolo Fiorina
Apr 18, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Moufida Ben Nasr, Paolo Fiorina
Mar 10, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Changyun HuLi Wen
Mar 17, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sandra Lord, Carla J Greenbaum
May 20, 2015·The Journal of Clinical Investigation·Jeffrey A BluestoneMark S Anderson
Dec 10, 2014·Digestive Diseases and Sciences·Aldo J Montano-Loza, Albert J Czaja
Apr 10, 2012·Human Vaccines & Immunotherapeutics·Eva d'Hennezel, Ciriaco A Piccirillo
Oct 30, 2013·Human Vaccines & Immunotherapeutics·Anna K E RydénMatthias G von Herrath
Oct 12, 2010·MAbs·Daniel R GettsStephen D Miller
Dec 9, 2014·Islets·Aarthi MagantiRaghavendra G Mirmira
Jan 13, 2010·MAbs·Janice M Reichert
Apr 24, 2010·Immunity·Brian StadinskiGeorge S Eisenbarth
Apr 24, 2010·Immunity·Xunrong LuoStephen D Miller
Mar 17, 2015·Journal of Autoimmunity·Ghanashyam SarikondaMatthias G von Herrath
Jan 28, 2015·Nature Reviews. Endocrinology·James C Reed, Kevan C Herold
Jun 15, 2010·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Mohamed Mabed
Jan 30, 2004·Diabetes·Chynna SteeleKevan C Herold
Nov 25, 2005·Diabetes·R Bottino, M Trucco
Aug 12, 2008·Diabetes·Paolo FiorinaMohamed H Sayegh
Jul 29, 2003·Diabetes Care·Zachary T Bloomgarden
Jun 23, 2012·Diabetes·S Alice LongDiabetes TrialNet and the Immune Tolerance Network
May 2, 2012·Diabetes Care·Jay M SosenkoDiabetes Prevention Trial-Type 1 Study Group
Apr 29, 2011·Diabetes·Mark A AtkinsonChristopher J Rhodes
Dec 31, 2008·Diabetes Care·Zachary T Bloomgarden
Feb 21, 2013·Diabetes·Jasmin LebastchiKevan C Herold
Jan 5, 2011·Diabetes·Jay S Skyler, Camillo Ricordi
Mar 1, 2007·Diabetes·Roberto MallonePeter van Endert
Nov 13, 2009·Diabetes Care·Simona CerneaPaolo Pozzilli
Oct 31, 2008·Diabetes·Massimo PietropaoloGeorge S Eisenbarth
Oct 26, 2013·Diabetes·Jay S Skyler
Oct 2, 2009·Diabetes·David M HarlanImmunology of Diabetes Society
May 11, 2016·Immunotherapy·Chantal Kuhn, Howard L Weiner
May 5, 2016·Expert Opinion on Biological Therapy·Chiara GuglielmiPaolo Pozzilli
Jun 3, 2016·Endocrinology, Diabetes & Metabolism Case Reports·Akira KurozumiYoshiya Tanaka
May 25, 2016·Journal of Autoimmunity·Chantal KuhnLucienne Chatenoud
Jun 28, 2016·Brain : a Journal of Neurology·Ryan C Winger, Scott S Zamvil
Apr 22, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Qi T YuKonstantinos A Papadakis
Aug 26, 2016·Current Diabetes Reports·Kimber M SimmonsAaron W Michels
Apr 8, 2009·The Journal of Allergy and Clinical Immunology·Makoto MiyaraShimon Sakaguchi
Nov 23, 2016·Scientific Reports·Clement ChanCarol Huang
Aug 16, 2016·Transfusion Medicine Reviews·Bernard Khor
Jul 9, 2016·Expert Review of Molecular Diagnostics·Johnny Ludvigsson
Mar 31, 2017·Nature Reviews. Disease Primers·Anastasia KatsarouAke Lernmark
May 10, 2017·Expert Opinion on Biological Therapy·Johnny Ludvigsson
Jul 13, 2004·Lancet·Mehboob A Hussain, Neil D Theise
Apr 4, 2017·Scientific Reports·Otoya UedaKou-Ichi Jishage
Sep 13, 2012·The Annals of Pharmacotherapy·Jessica W SkelleyJeffrey A Kyle
Feb 14, 2018·The Journal of Clinical Investigation·David A OstrovAaron W Michels
Oct 4, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Y Maurice MorillonRoland M Tisch
Jan 9, 2013·Nature Reviews. Endocrinology·Ake Lernmark, Helena Elding Larsson
Jan 29, 2014·Nature Reviews. Endocrinology·Bart O Roep, Timothy I M Tree
Sep 24, 2004·Diabetes/metabolism Research and Reviews·Amy E Juedes, Matthias G von Herrath
Jul 18, 2018·Diabetes Care·Michael J HallerType 1 Diabetes TrialNet ATG-GCSF Study Group
Nov 1, 2006·Circulation·Jörg J Goronzy, Cornelia M Weyand
Aug 13, 2009·European Journal of Immunology·Michael J HallerDesmond A Schatz
Aug 13, 2009·European Journal of Immunology·Matthias G von Herrath, Gerald Nepom
Nov 28, 2017·Current Opinion in Organ Transplantation·Ivica Grgic, Anil Chandraker
Dec 2, 2017·Current Opinion in Organ Transplantation·Sylvaine You, Lucienne Chatenoud
Oct 7, 2006·Diabetes/metabolism Research and Reviews·Volkert A L HuurmanBart O Roep
Oct 6, 2007·Diabetes/metabolism Research and Reviews·M ChianelliIMDIAB study group
Jul 18, 2009·Current Opinion in Organ Transplantation·Lucienne Chatenoud
Jan 26, 2010·Nature Reviews. Immunology·Bart O Roep, Mark Peakman
Feb 23, 2010·Nature Reviews. Endocrinology·Cristina Aguayo-Mazzucato, Susan Bonner-Weir
Feb 23, 2010·Nature Reviews. Endocrinology·Lucienne Chatenoud
Mar 24, 2010·Nature Reviews. Endocrinology·Aaron W Michels, Peter A Gottlieb
Apr 24, 2010·Nature Reviews. Immunology·Andrew C Chan, Paul J Carter
Oct 1, 2010·Current Opinion in Organ Transplantation·Sylvaine You, Lucienne Chatenoud
Oct 26, 2010·Nature Reviews. Immunology·Jeffrey A BluestoneLaurence A Turka
Mar 27, 2003·Nature Reviews. Immunology·Kathryn J Wood, Shimon Sakaguchi
Mar 27, 2003·Nature Reviews. Immunology·Matthias G von Herrath, Leonard C Harrison
Feb 4, 2003·Nature Reviews. Immunology·Lucienne Chatenoud
May 7, 2003·Gene Therapy·R BottinoN Giannoukakis
Mar 30, 2007·Clinical Pharmacology and Therapeutics·Jay S Skyler
Oct 30, 2015·Endocrinology·Colin M HyslopCarol Huang
Dec 1, 2007·Endocrine Reviews·Marc Y DonathThomas Mandrup-Poulsen
May 1, 2006·Expert Review of Clinical Immunology·Alberto Pugliese
Jan 1, 2007·Expert Review of Endocrinology & Metabolism·Antonella Maffei, Paul E Harris
Mar 1, 2007·Expert Review of Endocrinology & Metabolism·Christophe M Filippi, Matthias G von Herrath
Apr 27, 2019·Annals of the New York Academy of Sciences·Tijana Martinov, Brian T Fife
Mar 26, 2013·Nature Reviews. Immunology·Kevan C HeroldJeffrey A Bluestone
Sep 1, 2011·Nature Reviews. Endocrinology·Lucienne Chatenoud
Jan 1, 2008·Expert Review of Endocrinology & Metabolism·Carlos Eduardo Barra CouriJúlio César Voltarelli
Jul 1, 2009·Expert Review of Endocrinology & Metabolism·Alberto FalorniFausto Santeusanio
May 1, 2010·Nature·Jeffrey A BluestoneGeorge S Eisenbarth
Jan 22, 2009·Endocrine Research·Craig E Taplin, Jennifer M Barker
Apr 14, 2012·Journal of Atherosclerosis and Thrombosis·Naoto SasakiKen-ichi Hirata
Mar 4, 2015·The EMBO Journal·Bjarki JohannessonDieter Egli
Jun 11, 2019·The New England Journal of Medicine·Kevan C HeroldType 1 Diabetes TrialNet Study Group
Jun 11, 2019·The New England Journal of Medicine·Clifford J Rosen, Julie R Ingelfinger
Aug 1, 2015·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Mario R Ehlers
Jun 18, 2019·Diabetes/metabolism Research and Reviews·R David Leslie, Samuel T Jerram
Jun 3, 2016·Current Opinion in Endocrinology, Diabetes, and Obesity·Farooq Syed, Carmella Evans-Molina
Jan 21, 2011·Physiological Reviews·Tom L van BelleMatthias G von Herrath
Sep 27, 2019·Clinical and Experimental Immunology·W HaoCarla J Greenbaum
Jul 1, 2016·Current Opinion in Endocrinology, Diabetes, and Obesity·Jay M Sosenko
Jun 16, 2005·QJM : Monthly Journal of the Association of Physicians·P NarendranS Fourlanos
Dec 16, 2010·Human Vaccines·Mark C JohnsonRoland M Tisch
Jul 10, 2019·Statistical Applications in Genetics and Molecular Biology·Hong Zheng
Jun 18, 2014·Current Opinion in Endocrinology, Diabetes, and Obesity·James E Tooley, Kevan C Herold
Jul 2, 2014·Current Opinion in Endocrinology, Diabetes, and Obesity·Mark R Rigby, Mario R Ehlers
Apr 22, 2020·Medical Microbiology and Immunology·Kerry A McLaughlinMichael R Christie
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew E Schade, Alan D Levine
Dec 13, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshikatsu ShigiharaShosaku Narumi
Apr 29, 2008·Arquivos brasileiros de endocrinologia e metabologia·Melanie RodackiJosé Egídio Paulo de Oliveira
Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanfei HuangKarl L Womer
Feb 18, 2010·Current Opinion in Endocrinology, Diabetes, and Obesity·Mark R Rigby
Oct 9, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Brett J LoecheltType 1 Diabetes TrialNet Daclizumab/Mycophenolic Acid Study Group
Aug 30, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Li LiChristophe Benoist
Nov 7, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anabelle Visperas, Dario A A Vignali
Mar 6, 2017·Journal of Endocrinological Investigation·Davide FrumentoPaolo Fiorina
Feb 12, 2017·Frontiers in Pediatrics·Shamir CassimPascal Lapierre
Jul 19, 2017·Scientific Reports·Amy L ClarkFumihiko Urano
Sep 1, 2018·Frontiers in Immunology·Charles J KrogerRoland M Tisch
Jan 7, 2019·Diabetologia·Lucienne Chatenoud
Aug 14, 2020·F1000Research·Carla J Greenbaum, Carla J Greenbaum
Apr 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam P KohmStephen D Miller
Sep 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wen YangTerry L Delovitch
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xue-Zhong YuClaudio Anasetti
Mar 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Keisuke MinamimuraTakashi Maki
Sep 16, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Li LiRoland M Tisch
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jason J DevossMark S Anderson
Nov 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aaron W MichelsGeorge S Eisenbarth
Jul 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joana DuarteLuis Graca
Feb 3, 2015·The Journal of Clinical Investigation·Kevan C HeroldType 1 Diabetes TrialNet Study Group
Aug 20, 2016·Current Diabetes Reports·Raghavendra G MirmiraCarmella Evans-Molina
Oct 3, 2018·The Journal of Clinical Investigation·Baharak BahmaniReza Abdi
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