Oral anti‐CD3 monoclonal antibody delays diabetes in non‐obese diabetic (NOD) mice: effects on pregnancy and offspring—a preliminary report

Background The objective was to observe the effect of oral anti‐CD3 monoclonal antibody (mAb) on non‐obese diabetic mice, pregnancy, and offspring. Methods Three protocols are classified as: (1) Twenty non‐obese diabetic/ShiLtJ female mice were monitored for type 1 diabetes mellitus. If the blood glucose level was ≥ 250 mg/dL, the mice were treated for 8 days with either 50 or 100 µg oral anti‐CD3 monoclonal antibody. If the diabetes resolved, the mice were bred. (2) F1 offspring were monitored for diabetes; 15 female mice became diabetic. Non‐diabetic F1 female mice were divided into two groups [ten antibody (Ab) and ten control (C)] and bred. Ab female mice were given 100 µg monoclonal antibody before diabetes development and during pregnancy for 6 weeks. (3) Twenty‐five F2 Ab and 23 F2 C mice were monitored. At 15–17 weeks, Ab mice, both female and male, were given 100 µg monoclonal antibody for 8 weeks. Results (1) The diabetes in four female mice treated with 50 µg did not resolve; in three of the six diabetic female mice treated with 100 µg, the diabetes resolved and the mice were bred. The remaining ten non‐diabetic female mice were given 100 µg oral monoclonal antibody and then bred. No diabetes developed during pregnancy; 13 litters were born. (2) Three diabetic Ab female mice sustained their pregnancies versus one diabetic C female mouse ( p ≤ 0.05). (3) At 30 weeks, six Ab female and three Ab male mice and seven C female and three C male mice developed diabetes. The number of diabetic Ab and C mice was not different; diagnosis age was significantly different—Ab 23.3 ± 5.1 and C 18.8 ± 3.7 weeks ( p ≤ 0.05). Conclusions In female non‐obese diabetic mice, oral anti‐CD3 monoclonal antibody was effective in reversing diabetes and allowing pregnancy and extending longevity, but it did not prevent diabetes in the offspring. Copyright © 2011 John Wiley & Sons, Ltd.