Anti-CD3/anti-CXCL10 antibody combination therapy induces a persistent remission of type 1 diabetes in two mouse models
S Lasch, P Müller, M Bayer, JM Pfeilschifter… - Diabetes, 2015 - Am Diabetes Assoc
S Lasch, P Müller, M Bayer, JM Pfeilschifter, AD Luster, E Hintermann, U Christen
Diabetes, 2015•Am Diabetes AssocAnti-CD3 therapy of type 1 diabetes results in a temporary halt of its pathogenesis but does
not constitute a permanent cure. One problem is the reinfiltration of islets of Langerhans with
regenerated, autoaggressive lymphocytes. We aimed at blocking such a reentry by
neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and
NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of
diabetes and was superior to monotherapy with anti-CD3 or anti-CXCL10 alone. The …
not constitute a permanent cure. One problem is the reinfiltration of islets of Langerhans with
regenerated, autoaggressive lymphocytes. We aimed at blocking such a reentry by
neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and
NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of
diabetes and was superior to monotherapy with anti-CD3 or anti-CXCL10 alone. The …
Anti-CD3 therapy of type 1 diabetes results in a temporary halt of its pathogenesis but does not constitute a permanent cure. One problem is the reinfiltration of islets of Langerhans with regenerated, autoaggressive lymphocytes. We aimed at blocking such a reentry by neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of diabetes and was superior to monotherapy with anti-CD3 or anti-CXCL10 alone. The combination therapy prevented islet-specific T cells from reentering the islets of Langerhans and thereby blocked the autodestructive process. In addition, the local immune balance in the pancreas was shifted toward a regulatory phenotype. A sequential temporal inactivation of T cells and blockade of T-cell migration might constitute a novel therapy for patients with type 1 diabetes.
Am Diabetes Assoc