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High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model
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Trials in type 1 diabetes: Antigen-specific therapies

Ken T Coppieters1, Leonard C Harrison, Matthias G von Herrath

  • 1Type 1 Diabetes R&D Center, Novo Nordisk Inc., Seattle, WA, USA.

Clinical Immunology (Orlando, Fla.)
|March 16, 2013
PubMed

Type 1 diabetes (T1D) results from an aberrant immunological response against the insulin-producing beta cells in the islets of the pancreas. The ideal therapy would restore immune balance in a safe and lasting fashion, stopping the process of beta cell decay. The efficacy of immune suppressive agents such as cyclosporin underscores the notion that T1D can in principle be prevented, albeit at an unacceptable long-term safety risk. Immune modulatory drugs such as monoclonal anti-CD3 antibody, on the other hand, have recently had rather disappointing results in phase 3 trials, possibly due to inadequate dosing or choice of inappropriate endpoints. Therefore, it is argued that striking the right balance between safety and efficacy, together with careful trial design, will be paramount in preventing T1D. Here we outline the concept of antigen-specific tolerization as a strategy to safely induce long-term protection against T1D, focusing on available clinical trial data, key knowledge gaps and potential future directions.

Keywords:
Antigen-specific therapiesClinical trialsImmune interventionType 1 diabetes

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