title: Addition of rapamycin to anti-CD3 antibody improves long-term glycaemia control in diabetic NOD mice.
abstract: OBJECTIVE
  Non-Fc-binding Anti CD3 antibody has proven successful in reverting diabetes in the non-obese diabetes mouse model of type 1 diabetes and limited efficacy has been observed in human clinical trials. We hypothesized that addition of rapamycin, an mTOR inhibitor capable of inducing operational tolerance in allogeneic bone marrow transplantation, would result in improved diabetes reversal rates and overall glycemia.
  
  
  METHODS
  Seventy hyperglycemic non-obese diabetic mice were randomized to either a single injection of anti CD3 alone or a single injection of anti CD3 followed by 14 days of intra-peritoneal rapamycin. Mice were monitored for hyperglycemia and metabolic control.
  
  
  RESULTS
  Mice treated with the combination of anti CD3 and rapamycin had similar rates of diabetes reversal compared to anti CD3 alone (25/35 vs. 22/35). Mice treated with anti CD3 plus rapamycin had a significant improvement in glycemia control as exhibited by lower blood glucose levels in response to an intra-peritoneal glucose challenge; average peak blood glucose levels 30 min post intra-peritoneal injection of 2 gr/kg glucose were 6.9 mmol/L in the anti CD3 plus rapamycin group vs. 10 mmo/L in the anti CD3 alone (P<0.05).
  
  
  CONCLUSIONS
  The addition of rapamycin to anti CD3 results in significant improvement in glycaemia control in diabetic NOD mice.
authors.affiliation: Center for Human Immunology, NHLBI, NIH, Bethesda, Maryland, United States of America. perls@nhlbi.nih.gov
authors.forename: Shira
authors.initials: S
authors.lastname: Perl
authors.forename: Jordan
authors.initials: J
authors.lastname: Perlman
authors.forename: R P
authors.initials: RP
authors.lastname: Weitzel
authors.forename: Oswald
authors.initials: O
authors.lastname: Phang
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hsieh
authors.forename: John
authors.initials: J
authors.lastname: Tisdale
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D017252:CD3 Complex / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000188:drug therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D017252:CD3 Complex; D020123:Sirolimus