Addition of Rapamycin to Anti-CD3 Antibody Improves Long-Term Glycaemia Control in Diabetic NOD Mice |
| |
| Authors: | Shira Perl Jordan Perlman R P Weitzel Oswald Phang Matthew M Hsieh John Tisdale |
| |
| Institution: | 1. Center for Human Immunology, NHLBI, NIH, Bethesda, Maryland, United States of America.; 2. Molecular and Clinical Hematology Branch, NHLBI, NIH, Bethesda, Maryland, United States of America.; La Jolla Institute for Allergy and Immunology, United States of America, |
| |
| Abstract: | Aims/HypothesisNon-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.MethodsSeventy 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.ResultsMice 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/InterpretationThe addition of rapamycin to anti CD3 results in significant improvement in glycaemia control in diabetic NOD mice. |
| |
| Keywords: | |
|
|
