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.
abstract: Oral administration of anti-CD3 antibodies induced regulatory T cells (Tregs) alleviating the insulin resistance and liver damage in animal models.
  
  
  OBJECTIVE
  To determine the safety and biological effects of oral OKT3 monoclonal antibody (Balashov et al. Neurology 55:192-8, 2000) in patients with NASH.
  
  
  METHODS
  In this Phase-IIa trial, four groups of patients with biopsy-proven NASH (n = 9/group) received placebo (group A) or oral OKT3 (group B: 0.2; C: 1.0; D: 5.0 mg/day) for 30 days. Patients were followed for safety, liver enzymes, glucose, lipid profile, oral glucose tolerance test (OGTT), serum cytokines and Tregs.
  
  
  RESULTS
  Oral OKT3 was well tolerated without treatment-related adverse events. OKT3 induced Tregs: with significant increases of CD4(+)LAP(+) (Latency associated peptide) and CD4(+)CD25(+)LAP(+) cells in Group D, and a significant increase in TGF-β in Groups C and D. AST decreased significantly in group D and a trend in Groups B and C. Fasting plasma glucose decreased significantly in all treatment groups compared with placebo. OGTT decreased significantly in Group D. Correlations were observed between the changes in several immune-modulatory effects and clinical biomarkers. While serum anti-CD3 levels where undetectable increases in human anti-mouse antibody levels were observed in Groups C and D.
  
  
  CONCLUSIONS
  Oral administration of anti-CD3 MAb to patients with NASH was safe and well tolerated. Positive biological effects were noted in several hepatic, metabolic and immunologic parameters. These findings provide the basis for future trials to investigate the effect of oral anti-CD3 MAb immunotherapy in patients with NASH.
authors: Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Gadi
authors: G
authors: Lalazar
authors: Meir
authors: M
authors: Mizrahi
authors: Ilit
authors: I
authors: Turgeman
authors: Tomer
authors: T
authors: Adar
authors: Ami
authors: A
authors: Ben Ya'acov
authors: Yehudit
authors: Y
authors: Shabat
authors: Assy
authors: A
authors: Nimer
authors: Nila
authors: N
authors: Hemed
authors: Lidya
authors: L
authors: Zolotarovya
authors: Yoav
authors: Y
authors: Lichtenstein
authors: Nadya
authors: N
authors: Lisovoder
authors: Sarit
authors: S
authors: Samira
authors: Itamar
authors: I
authors: Shalit
authors: Ronald
authors: R
authors: Ellis
authors: Yaron
authors: Y
authors: Ilan
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers; D015897:Comorbidity; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016853:Muromonab-CD3