{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:14:36Z","timestamp":1790396076363,"version":"4.1.0"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"The Roman-Epstein Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,21]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>The immune system plays a role in the pathogenesis of non-alcoholic steatohepatitis (NASH) underlying hepatocyte injury and fibrosis progression at all disease stages. Oral administration of anti-CD3 monoclonal antibody (mAb) has been shown in preclinical studies to be an effective method for systemic immune modulation and alleviates immune-mediated disorders without T cell depletion. In the present review, we summarize the concept of the oral administration of humanized anti-CD3 mAb in patients with NASH and discuss the potential of this treatment to address the current requirements of treatments for NASH. Recently published preclinical and clinical data on oral administration of anti CD3 are discussed. Human trials have shown that the oral administration of anti-CD3 in healthy volunteers, patients with chronic hepatitis C virus (HCV) infection and patients with NASH and type 2 diabetes is safe and well tolerated, as well as biologically active. Oral anti-CD3 induces regulatory T cells, suppresses the chronic inflammatory state associated with NASH and exerts a beneficial effect on clinically relevant parameters. Foralumab is a fully human anti-CD3 mAb that has recently been shown to exert a potent anti-inflammatory effect in humanized mice. It is being developed for treatment of NASH and primary biliary cholangitis (PBC). Oral administration of anti CD3 may provide an effective therapy for patients with NASH.<\/jats:p>","DOI":"10.1111\/cei.13159","type":"journal-article","created":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T17:15:27Z","timestamp":1529428527000},"page":"275-283","source":"Crossref","is-referenced-by-count":43,"title":["Immunotherapy with oral administration of humanized anti-CD3 monoclonal antibody: a novel gut-immune system-based therapy for metaflammation and NASH"],"prefix":"10.1093","volume":"193","author":[{"given":"Y","family":"Ilan","sequence":"first","affiliation":[{"name":"Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Shailubhai","sequence":"additional","affiliation":[{"name":"Tiziana Life Sciences, R& D Center, Doylestown, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, VCU School of Medicine, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,9,21]]},"reference":[{"key":"2021120808383562500_cei13159-bib-0001","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S2468-1253(16)30011-5","article-title":"Pathogenesis and novel treatment options for non-alcoholic steatohepatitis","volume":"1","author":"Wong","year":"2016","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2021120808383562500_cei13159-bib-0002","doi-asserted-by":"crossref","first-page":"425021","DOI":"10.1155\/2012\/425021","article-title":"Induction of immunological tolerance by oral anti-CD3","volume":"2012","author":"da Cunha","year":"2012","journal-title":"Clin Dev Immunol"},{"key":"2021120808383562500_cei13159-bib-0003","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nrd.2015.3","article-title":"Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies","volume":"15","author":"Musso","year":"2016","journal-title":"Nat Rev Drug Discov"},{"key":"2021120808383562500_cei13159-bib-0004","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1111\/liv.13270","article-title":"The therapeutic landscape of non-alcoholic steatohepatitis","volume":"37","author":"Perazzo","year":"2017","journal-title":"Liver Int"},{"key":"2021120808383562500_cei13159-bib-0005","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1136\/gutjnl-2016-312431","article-title":"Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease","volume":"66","author":"Rotman","year":"2017","journal-title":"Gut"},{"key":"2021120808383562500_cei13159-bib-0006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4093\/dmj.2016.40.1.1","article-title":"Novel molecular mechanisms in the development of non-alcoholic steatohepatitis","volume":"40","author":"Povero","year":"2016","journal-title":"Diabetes Metab J"},{"key":"2021120808383562500_cei13159-bib-0007","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.4254\/wjh.v7.i15.1905","article-title":"Cross talk of the immune system in the adipose tissue and the liver in non-alcoholic steatohepatitis: pathology and beyond","volume":"7","author":"Vonghia","year":"2015","journal-title":"World J Hepatol"},{"key":"2021120808383562500_cei13159-bib-0008","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11154-016-9339-2","article-title":"The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH)","volume":"17","author":"Nati","year":"2016","journal-title":"Rev Endocr Metab Disord"},{"key":"2021120808383562500_cei13159-bib-0009","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1194\/jlr.R066514","article-title":"Lipid signaling and lipotoxicity in metaflammation: indications for metabolic disease pathogenesis and treatment","volume":"57","author":"Ertunc","year":"2016","journal-title":"J Lipid Res"},{"key":"2021120808383562500_cei13159-bib-0010","doi-asserted-by":"crossref","first-page":"5170402","DOI":"10.1155\/2016\/5170402","article-title":"Pathogenesis of nonalcoholic steatohepatitis: interactions between liver parenchymal and nonparenchymal cells","volume":"2016","author":"Magee","year":"2016","journal-title":"Biomed Res Int"},{"key":"2021120808383562500_cei13159-bib-0011","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nrendo.2012.114","article-title":"Adaptive immunity in obesity and insulin resistance","volume":"8","author":"Sell","year":"2012","journal-title":"Nat Rev Endocrinol"},{"key":"2021120808383562500_cei13159-bib-0012","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrgastro.2010.21","article-title":"Pathology of nonalcoholic fatty liver disease","volume":"7","author":"Brunt","year":"2010","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2021120808383562500_cei13159-bib-0013","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/hep.26937","article-title":"The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease","volume":"59","author":"Gadd","year":"2014","journal-title":"Hepatology"},{"key":"2021120808383562500_cei13159-bib-0014","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1365-2249.2011.04471.x","article-title":"Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease","volume":"166","author":"Tang","year":"2011","journal-title":"Clin Exp Immunol"},{"key":"2021120808383562500_cei13159-bib-0015","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1002\/hep.26746","article-title":"IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice","volume":"59","author":"Harley","year":"2014","journal-title":"Hepatology"},{"key":"2021120808383562500_cei13159-bib-0016","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4049\/jimmunol.1501175","article-title":"Progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis is marked by a higher frequency of Th17 cells in the liver and an increased Th17\/resting regulatory T cell ratio in peripheral blood and in the liver","volume":"196","author":"Rau","year":"2016","journal-title":"J Immunol"},{"key":"2021120808383562500_cei13159-bib-0017","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/s00018-013-1486-y","article-title":"B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance","volume":"71","author":"Winer","year":"2014","journal-title":"Cell Mol Life Sci"},{"key":"2021120808383562500_cei13159-bib-0018","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12865-017-0215-y","article-title":"The imbalance of Th17\/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice","volume":"18","author":"He","year":"2017","journal-title":"BMC Immunol"},{"key":"2021120808383562500_cei13159-bib-0019","doi-asserted-by":"crossref","first-page":"490","DOI":"10.3389\/fimmu.2016.00490","article-title":"Immune imbalances in non-alcoholic fatty liver disease: from general biomarkers and neutrophils to interleukin-17 axis activation and new therapeutic targets","volume":"7","author":"Paquissi","year":"2016","journal-title":"Front Immunol"},{"key":"2021120808383562500_cei13159-bib-0020","doi-asserted-by":"crossref","first-page":"4652","DOI":"10.3748\/wjg.v16.i37.4652","article-title":"Roles of liver innate immune cells in nonalcoholic fatty liver disease","volume":"16","author":"Zhan","year":"2010","journal-title":"World J Gastroenterol"},{"key":"2021120808383562500_cei13159-bib-0021","doi-asserted-by":"crossref","first-page":"127","DOI":"10.5114\/ceh.2017.68466","article-title":"The interplay between Th17 and T-regulatory responses as well as adipokines in the progression of non-alcoholic fatty liver disease","volume":"3","author":"\u015awiderska","year":"2017","journal-title":"Clin Exp Hepatol"},{"key":"2021120808383562500_cei13159-bib-0022","doi-asserted-by":"crossref","first-page":"453","DOI":"10.2131\/jts.32.453","article-title":"Common pathogenic mechanism in development progression of liver injury caused by non-alcoholic or alcoholic steatohepatitis","volume":"32","author":"Nagata","year":"2007","journal-title":"J Toxicol Sci"},{"key":"2021120808383562500_cei13159-bib-0023","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1111\/apt.13833","article-title":"Review article: novel methods for the treatment of non-alcoholic steatohepatitis \u2013 targeting the gut immune system to decrease the systemic inflammatory response without immune suppression","volume":"44","author":"Ilan","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"key":"2021120808383562500_cei13159-bib-0024","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1038\/cti.2015.47","article-title":"Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease","volume":"5","author":"Ilan","year":"2016","journal-title":"Clin Transl Immunol"},{"key":"2021120808383562500_cei13159-bib-0025","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1097\/MCG.0b013e31827873dc","article-title":"Immune therapy for nonalcoholic steatohepatitis: are we there yet?","volume":"47","author":"Ilan","year":"2013","journal-title":"J Clin Gastroenterol"},{"key":"2021120808383562500_cei13159-bib-0026","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.molimm.2003.11.017","article-title":"Molecular mechanisms for the assembly of the T cell receptor\u2013CD3 complex","volume":"40","author":"Call","year":"2004","journal-title":"Mol Immunol"},{"key":"2021120808383562500_cei13159-bib-0027","first-page":"29","article-title":"Molecular dissection of the T-cell receptor\/CD3 complex","volume":"59","author":"Malissen","year":"1993","journal-title":"Immunol Ser"},{"key":"2021120808383562500_cei13159-bib-0028","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1097\/00007890-199909150-00003","article-title":"Phase I trial of a humanized, Fc receptor nonbinding OKT3 antibody, huOKT3gamma1(Ala-Ala) in the treatment of acute renal allograft rejection","volume":"68","author":"Woodle","year":"1999","journal-title":"Transplantation"},{"key":"2021120808383562500_cei13159-bib-0029","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1097\/00007890-199912150-00005","article-title":"Phase I study of an engineered aglycosylated humanized CD3 antibody in renal transplant rejection","volume":"68","author":"Friend","year":"1999","journal-title":"Transplantation"},{"key":"2021120808383562500_cei13159-bib-0030","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nri1000","article-title":"CD3-specific antibody-induced active tolerance: from bench to bedside","volume":"3","author":"Chatenoud","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"2021120808383562500_cei13159-bib-0031","first-page":"279\u201386; discussion: 286\u201390","article-title":"CD3 antibody treatment stimulates the functional capability of regulatory T cells","volume":"252","author":"Chatenoud","year":"2003","journal-title":"Novartis Found Symp"},{"key":"2021120808383562500_cei13159-bib-0032","doi-asserted-by":"crossref","first-page":"457","DOI":"10.2337\/diab.41.4.457","article-title":"Anti-CD3 immunotoxin prevents low-dose STZ\/interferon-induced autoimmune diabetes in mouse","volume":"41","author":"Vallera","year":"1992","journal-title":"Diabetes"},{"key":"2021120808383562500_cei13159-bib-0033","doi-asserted-by":"crossref","first-page":"448","DOI":"10.2337\/db15-1625","article-title":"Reversal of diabetes in NOD mice by clinical-grade proinsulin and IL-10-secreting lactococcus lactis in combination with low-dose anti-CD3 depends on the induction of Foxp3-positive T cells","volume":"66","author":"Takiishi","year":"2017","journal-title":"Diabetes"},{"key":"2021120808383562500_cei13159-bib-0034","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.clim.2013.05.001","article-title":"Anti-CD3 clinical trials in type 1 diabetes mellitus","volume":"149","author":"Daifotis","year":"2013","journal-title":"Clin Immunol"},{"key":"2021120808383562500_cei13159-bib-0035","first-page":"1907","article-title":"Modified anti-CD3 therapy in psoriatic arthritis: a phase I\/II clinical trial","volume":"29","author":"Utset","year":"2002","journal-title":"J Rheumatol"},{"key":"2021120808383562500_cei13159-bib-0036","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/ibd.21084","article-title":"Prospective randomized open-label multicenter phase I\/II dose escalation trial of visilizumab (HuM291) in severe steroid-refractory ulcerative colitis","volume":"16","author":"Baumgart","year":"2010","journal-title":"Inflamm Bowel Dis"},{"key":"2021120808383562500_cei13159-bib-0037","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1053\/j.gastro.2007.08.035","article-title":"A phase I study of visilizumab, a humanized anti-CD3 monoclonal antibody, in severe steroid-refractory ulcerative colitis","volume":"133","author":"Plevy","year":"2007","journal-title":"Gastroenterology"},{"key":"2021120808383562500_cei13159-bib-0038","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1136\/gut.2009.205443","article-title":"Anti-CD3 antibody visilizumab is not effective in patients with intravenous corticosteroid-refractory ulcerative colitis","volume":"59","author":"Sandborn","year":"2010","journal-title":"Gut"},{"key":"2021120808383562500_cei13159-bib-0039","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1056\/NEJMoa043980","article-title":"Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes","volume":"352","author":"Keymeulen","year":"2005","journal-title":"N Engl J Med"},{"key":"2021120808383562500_cei13159-bib-0040","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.2337\/diabetes.54.6.1763","article-title":"A single course of anti-CD3 monoclonal antibody hOKT3{gamma}1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes","volume":"54","author":"Herold","year":"2005","journal-title":"Diabetes"},{"key":"2021120808383562500_cei13159-bib-0041","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1056\/NEJMoa012864","article-title":"Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus","volume":"346","author":"Herold","year":"2002","journal-title":"N Engl J Med"},{"key":"2021120808383562500_cei13159-bib-0042","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0167-5699(86)90028-9","article-title":"The immune response against therapeutic monoclonal antibodies","volume":"7","author":"Chatenoud","year":"1986","journal-title":"Immunol Today"},{"key":"2021120808383562500_cei13159-bib-0043","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1126\/science.3086976","article-title":"The human immune response to the OKT3 monoclonal antibody is oligoclonal","volume":"232","author":"Chatenoud","year":"1986","journal-title":"Science"},{"key":"2021120808383562500_cei13159-bib-0044","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1002\/eji.1830250603","article-title":"Fc receptor binding of anti-CD3 monoclonal antibodies is not essential for immunosuppression, but triggers cytokine-related side effects","volume":"25","author":"Vossen","year":"1995","journal-title":"Eur J Immunol"},{"key":"2021120808383562500_cei13159-bib-0045","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1046\/j.1365-3083.2000.00723.x","article-title":"Anti-CD3 induced thymocyte apoptosis in vivo require the antibody Fc domain","volume":"51","author":"Xue","year":"2000","journal-title":"Scand J Immunol"},{"key":"2021120808383562500_cei13159-bib-0046","first-page":"437","article-title":"Monoclonal antibodies to CD3 as immunosuppressants","volume":"2","author":"Chatenoud","year":"1990","journal-title":"Semin Immunol"},{"key":"2021120808383562500_cei13159-bib-0047","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1097\/00007890-199010000-00023","article-title":"Reduction of morbidity and cytokine release in anti-CD3 MoAb-treated mice by corticosteroids","volume":"50","author":"Ferran","year":"1990","journal-title":"Transplantation"},{"key":"2021120808383562500_cei13159-bib-0048","first-page":"1922","article-title":"In vivo T lymphocyte activation induced in mice following the injection of anti-CD3 monoclonal antibody","volume":"22","author":"Ferran","year":"1990","journal-title":"Transplant Proc"},{"key":"2021120808383562500_cei13159-bib-0049","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/BF02063942","article-title":"Immunomodulation of transplant rejection using monoclonal antibodies and soluble receptors","volume":"40","author":"Alegre","year":"1995","journal-title":"Dig Dis Sci"},{"key":"2021120808383562500_cei13159-bib-0050","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1900\/RDS.2012.9.372","article-title":"CD3 monoclonal antibodies: a first step towards operational immune tolerance in the clinic","volume":"9","author":"Chatenoud","year":"2012","journal-title":"Rev Diabet Stud"},{"key":"2021120808383562500_cei13159-bib-0051","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/eji.201545708","article-title":"Changes in T-cell subsets identify responders to FcR-nonbinding anti-CD3 mAb (teplizumab) in patients with type 1 diabetes","volume":"46","author":"Tooley","year":"2016","journal-title":"Eur J Immunol"},{"key":"2021120808383562500_cei13159-bib-0052","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1517\/14712598.2014.881797","article-title":"Treatment of new onset type 1 diabetes with teplizumab: successes and pitfalls in development","volume":"14","author":"Vudattu","year":"2014","journal-title":"Expert Opin Biol Ther"},{"key":"2021120808383562500_cei13159-bib-0053","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0140-6736(11)60931-8","article-title":"Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial","volume":"378","author":"Sherry","year":"2011","journal-title":"Lancet"},{"key":"2021120808383562500_cei13159-bib-0054","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1080\/14712598.2016.1180363","article-title":"Efficacy and safety of otelixizumab use in new-onset type 1 diabetes mellitus","volume":"16","author":"Guglielmi","year":"2016","journal-title":"Expert Opin Biol Ther"},{"key":"2021120808383562500_cei13159-bib-0055","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1055\/s-0042-101241","article-title":"Subcutaneous administration of otelixizumab is limited by injection site reactions: results of an exploratory study in type 1 diabetes mellitus patients","volume":"124","author":"MacDonald","year":"2016","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"2021120808383562500_cei13159-bib-0056","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/nm924","article-title":"TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes","volume":"9","author":"Belghith","year":"2003","journal-title":"Nat Med"},{"key":"2021120808383562500_cei13159-bib-0057","doi-asserted-by":"crossref","first-page":"6335","DOI":"10.1073\/pnas.0701171104","article-title":"Adaptive TGF-beta-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment","volume":"104","author":"You","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021120808383562500_cei13159-bib-0058","doi-asserted-by":"crossref","first-page":"eaai7793","DOI":"10.1126\/sciimmunol.aai7793","article-title":"Partially exhausted CD8 T cells are associated with clinical response to teplizumab in new-onset type 1 diabetes","volume":"1","author":"Long","year":"2016","journal-title":"Sci Immunol"},{"key":"2021120808383562500_cei13159-bib-0059","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1172\/JCI23961","article-title":"TCR stimulation with modified anti-CD3 mAb expands CD8 T cell population and induces CD8CD25 Tregs","volume":"115","author":"Bisikirska","year":"2005","journal-title":"J Clin Invest"},{"key":"2021120808383562500_cei13159-bib-0060","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.2337\/db13-0236","article-title":"Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protege trial","volume":"62","author":"Hagopian","year":"2013","journal-title":"Diabetes"},{"key":"2021120808383562500_cei13159-bib-0061","doi-asserted-by":"crossref","first-page":"889","DOI":"10.2217\/imt-2016-0049","article-title":"Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside","volume":"8","author":"Kuhn","year":"2016","journal-title":"Immunotherapy"},{"key":"2021120808383562500_cei13159-bib-0062","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1600-065X.2011.01017.x","article-title":"Oral tolerance","volume":"241","author":"Weiner","year":"2011","journal-title":"Immunol Rev"},{"key":"2021120808383562500_cei13159-bib-0063","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nature10228","article-title":"Control of TH17 cells occurs in the small intestine","volume":"475","author":"Esplugues","year":"2011","journal-title":"Nature"},{"key":"2021120808383562500_cei13159-bib-0064","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nm1408","article-title":"Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4\u00b1 CD25\u2013 LAP\u00b1 T cells","volume":"12","author":"Ochi","year":"2006","journal-title":"Nat Med"},{"key":"2021120808383562500_cei13159-bib-0065","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jns.2008.07.027","article-title":"New immunosuppressive approaches: oral administration of CD3-specific antibody to treat autoimmunity","volume":"274","author":"Ochi","year":"2008","journal-title":"J Neurol Sci"},{"key":"2021120808383562500_cei13159-bib-0066","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.2337\/db06-1632","article-title":"Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody","volume":"56","author":"Ishikawa","year":"2007","journal-title":"Diabetes"},{"key":"2021120808383562500_cei13159-bib-0067","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.4049\/jimmunol.167.8.4245","article-title":"Activation of CD25(\u00b1)CD4(\u00b1) regulatory T cells by oral antigen administration","volume":"167","author":"Zhang","year":"2001","journal-title":"J Immunol"},{"key":"2021120808383562500_cei13159-bib-0068","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jaut.2016.10.001","article-title":"Mucosal administration of CD3-specific monoclonal antibody inhibits diabetes in NOD mice and in a preclinical mouse model transgenic for the CD3 epsilon chain","volume":"76","author":"Kuhn","year":"2017","journal-title":"J Autoimmun"},{"key":"2021120808383562500_cei13159-bib-0069","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1053\/j.gastro.2012.07.019","article-title":"An oral CD3-specific antibody suppresses T-cell-induced colitis and alters cytokine responses to T-cell activation in mice","volume":"143","author":"Forster","year":"2012","journal-title":"Gastroenterology"},{"key":"2021120808383562500_cei13159-bib-0070","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1161\/CIRCULATIONAHA.109.863431","article-title":"Oral anti-CD3 antibody treatment induces regulatory T cells and inhibits the development of atherosclerosis in mice","volume":"120","author":"Sasaki","year":"2009","journal-title":"Circulation"},{"key":"2021120808383562500_cei13159-bib-0071","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.clim.2008.08.028","article-title":"Induction of mucosal tolerance in SLE: a sniff or a sip away from ameliorating lupus?","volume":"130","author":"Wu","year":"2009","journal-title":"Clin Immunol"},{"key":"2021120808383562500_cei13159-bib-0072","doi-asserted-by":"crossref","first-page":"6038","DOI":"10.4049\/jimmunol.181.9.6038","article-title":"Nasal anti-CD3 antibody ameliorates lupus by inducing an IL-10-secreting CD4\u00b1 CD25- LAP\u00b1 regulatory T cell and is associated with down-regulation of IL-17\u00b1 CD4\u00b1 ICOS\u00b1 CXCR72\u00b1 follicular helper T cells","volume":"181","author":"Wu","year":"2008","journal-title":"J Immunol"},{"key":"2021120808383562500_cei13159-bib-0073","doi-asserted-by":"crossref","first-page":"118ra12","DOI":"10.1126\/scitranslmed.3003401","article-title":"Teplizumab induces human gut-tropic regulatory cells in humanized mice and patients","volume":"4","author":"Waldron-Lynch","year":"2012","journal-title":"Sci Transl Med"},{"key":"2021120808383562500_cei13159-bib-0074","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s10875-009-9323-7","article-title":"Oral administration of OKT3 monoclonal antibody to human subjects induces a dose-dependent immunologic effect in T cells and dendritic cells","volume":"30","author":"Ilan","year":"2010","journal-title":"J Clin Immunol"},{"key":"2021120808383562500_cei13159-bib-0075","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/jvh.12369","article-title":"Oral anti-CD3 immunotherapy for HCV-nonresponders is safe, promotes regulatory T cells and decreases viral load and liver enzyme levels: results of a phase-2a placebo-controlled trial","volume":"22","author":"Halota","year":"2015","journal-title":"J Viral Hepatol"},{"key":"2021120808383562500_cei13159-bib-0076","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1053\/j.gastro.2015.05.044","article-title":"Association of adipose tissue inflammation with histologic severity of nonalcoholic fatty liver disease","volume":"149","author":"du Plessis","year":"2015","journal-title":"Gastroenterology"},{"key":"2021120808383562500_cei13159-bib-0077","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.canlet.2011.10.017","article-title":"Recent trends in antibody-based oncologic imaging","volume":"315","author":"Kaur","year":"2012","journal-title":"Cancer Lett"},{"key":"2021120808383562500_cei13159-bib-0078","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.jhep.2013.03.033","article-title":"Decoding cell death signals in liver inflammation","volume":"59","author":"Brenner","year":"2013","journal-title":"J Hepatol"},{"key":"2021120808383562500_cei13159-bib-0079","doi-asserted-by":"crossref","first-page":"G1102","DOI":"10.1152\/ajpgi.00095.2016","article-title":"Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance","volume":"310","author":"Ilan","year":"2016","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2021120808383562500_cei13159-bib-0080","doi-asserted-by":"crossref","first-page":"9765","DOI":"10.1073\/pnas.0908771107","article-title":"Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob\/ob mice","volume":"107","author":"Ilan","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021120808383562500_cei13159-bib-0081","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s10875-015-0160-6","article-title":"Oral administration of OKT3 MAb to patients with NASH, promotes regulatory T-cell induction, and alleviates insulin resistance: results of a phase IIa blinded placebo-controlled trial","volume":"35","author":"Lalazar","year":"2015","journal-title":"J Clin Immunol"},{"key":"2021120808383562500_cei13159-bib-0082","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.clim.2017.07.005","article-title":"Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice","volume":"183","author":"Ogura","year":"2017","journal-title":"Clin Immunol"},{"key":"2021120808383562500_cei13159-bib-0083","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00125-012-2753-4","article-title":"Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial","volume":"56","author":"Herold","year":"2013","journal-title":"Diabetologia"},{"key":"2021120808383562500_cei13159-bib-0084","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1111\/j.1600-6143.2012.04178.x","article-title":"Analysis of human biologics with a mouse skin transplant model in humanized mice","volume":"12","author":"Waldron-Lynch","year":"2012","journal-title":"Am J Transplant"},{"key":"2021120808383562500_cei13159-bib-0085","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.2337\/db13-0345","article-title":"Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders","volume":"62","author":"Herold","year":"2013","journal-title":"Diabetes"},{"key":"2021120808383562500_cei13159-bib-0086","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.4049\/jimmunol.1000836","article-title":"Mucosal anti-CD3 monoclonal antibody attenuates collagen-induced arthritis that is associated with induction of LAP\u00b1 regulatory T cells and is enhanced by administration of an emulsome-based Th2-skewing adjuvant","volume":"185","author":"Wu","year":"2010","journal-title":"J Immunol"},{"key":"2021120808383562500_cei13159-bib-0087","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1177\/0961203308100511","article-title":"Suppression of murine SLE by oral anti-CD3: inducible CD4\u00b1CD25-LAP\u00b1 regulatory T cells control the expansion of IL-17\u00b1 follicular helper T cells","volume":"18","author":"Wu","year":"2009","journal-title":"Lupus"},{"key":"2021120808383562500_cei13159-bib-0088","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/intimm\/13.6.825","article-title":"Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes","volume":"13","author":"Slavin","year":"2001","journal-title":"Int Immunol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.13159","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/193\/3\/275\/41645418\/cei13159.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/193\/3\/275\/41645418\/cei13159.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T16:25:58Z","timestamp":1641054358000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/193\/3\/275\/6411908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9]]},"references-count":88,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,9,21]]},"published-print":{"date-parts":[[2018,9,21]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.13159","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,9]]},"published":{"date-parts":[[2018,9]]}}}