Anti-CD3 Antibody for the Prevention of Type 1 Diabetes: A Story of Perseverance.

Type 1 diabetes (T1D) is an autoimmune disease characterized by an insulin deficiency. Ever since the discovery of insulin almost 100 years ago, patients with T1D have relied on multiple daily insulin injections to survive an otherwise deadly disease. Despite decades of research and clinical trials, no treatment exists yet to prevent or cure T1D. A recent prevention trial using the anti-CD3 antibody teplizumab in individuals at a high risk of developing T1D has provided the first piece of evidence that a safe and transient intervention may be able to delay disease. In this Perspective, we review the 40-year long history of anti-CD3 and discuss how this antibody became a candidate for the treatment of autoimmune diabetes. The path that leads to its use in this latest clinical trial for T1D has been winding and strewn with setbacks. The molecular actions of the anti-CD3 antibody that target T lymphocytes are well-understood, but its systemic effect on immune function has proven more difficult to unravel. Moreover, preclinical data suggested that the utility of anti-CD3 for the prevention of T1D may be limited. However, the latest clinical data are encouraging and exemplify how a basic discovery can, decades later and with much perseverance, become a promising therapeutic candidate.