Towards a curative therapy in type 1 diabetes: remission of autoimmunity, maintenance and augmentation of beta cell mass.
Recent clinical trials have shown that the loss of insulin production that characterizes progressive type 1 diabetes mellitus can be attenuated by treatment with non-FcR binding anti-CD3 monoclonal antibody (mAb). This approach is a first step towards the ultimate goals of treatment: to improve and maintain insulin production. However, additional interventions will be needed because, with time, there is progressive loss of insulin production after treatment with a single course of anti-CD3 mAb. The basis for the long-term loss of insulin production after immune therapy is not known because animal models have not been informative about the mechanisms, and there are not biomarkers of autoimmunity that can be used to monitor the process. Therefore, strategies for clinical testing might involve both beta cell and immunological therapies. Examples of the former include agents such as GLP1 receptor agonists or DPPIV inhibitors which increase beta cell insulin content. Preclinical data suggest that co-administration of antigen with anti-CD3 mAb can induce a tolerogenic response to the antigen that may then be administered to maintain tolerance. In addition, other immunological approaches as well as interventions earlier in the disease process may be successful in maintaining greater beta cell function for extended periods.
Waldron-Lynch
Frank
F
Department of Medicine, University College Hospital, Galway, Ireland.
von Herrath
Matthias
M
Herold
Kevan C
KC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D006801:Humans; D007108:Immune Tolerance; D007155:Immunologic Factors / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D007328:Insulin / Q000276:immunology* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007155:Immunologic Factors; D007328:Insulin; D052216:Glucagon-Like Peptide 1