CD3-specific antibodies to restore tolerance in autoimmune diabetes

The identification of type 1 diabetes as an immune-mediated disease rapidly led to immune intervention approaches. Innovative randomized trials, mostly placebo controlled, were conducted based on data from animal studies. Results were variable but major proof of concept emerged from these trials. That is exactly the case with CD3-specific monoclonal antibodies whose usage in new onset diabetic patients provided very promising results in terms of preservation of pancreatic β-cell mass and function. CD3 antibody therapy showed that it was possible to obtain a long-term therapeutic effect following short course administration of a biological agent promoting immune regulation. The next sensible step to go for is to improve the usage of CD3 antibody in terms of safety and effectiveness over the long term. The proposal would be to combine CD3 antibodies with strategies targeting the different actors of the immune and inflammatory responses (β cells, antigen presenting cells and T lymphocytes).

Section editors:Michel Goldman – Innovative Medicines Initiative, COV2, Brussels, BelgiumLucienne Chatenoud – Inserm U1013, Paris, France