Mechanisms mediating anti-CD3 antibody efficacy: insights from a mathematical model of type 1 diabetes.
Anti-CD3 antibody therapy, a promising clinical approach for the treatment of type 1 diabetes (T1D), was investigated using a mathematical model of T1D in the female nonobese diabetic (NOD) mouse. Analyses of model simulation results indicate that, in addition to the known direct effects of anti-CD3 antibody on T lymphocytes, two additional mechanisms are required for sustained disease remission: (a) rapid regrowth of healthy beta cells following clearance of islet inflammation and (b) enhanced regulatory T cell activity and/or phenotypic changes in antigen presenting cells (APCs) that promote a stable regulatory environment in the pancreas.
Young
Daniel L
DL
Entelos Inc., 110 Marsh Drive, Foster City, CA 94404, USA.
Ramanujan
Saroja
S
Kreuwel
Huub T C
HT
Whiting
Chan Chung
CC
Gadkar
Kapil G
KG
Shoda
Lisl K M
LK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D000938:Antigen-Presenting Cells / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology*; D003198:Computer Simulation; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D050417:Insulin-Secreting Cells / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D008962:Models, Theoretical; D049490:Systems Biology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D017252:CD3 Complex