CD3-specific antibodies as promising tools to aim at immune tolerance in the clinic

Currently, therapies applied in transplantation and autoimmunity are essentially based on the use of immunosuppressants. These agents depress all immune responses and expose individuals to the recurrence of the pathogenic immune process once they are withdrawn, thus necessitating a chronic administration leading to the risk of recurrent infections and increased frequency of tumors. At variance, CD3 monoclonal antibodies appear unique in their capacity to induce immunological tolerance that is an antigen-specific unresponsiveness in the absence of chronic immunosuppression. This has been well-established in experimental models, and recent data show successful clinical translation using humanized anti-CD3 antibodies. The aim of this brief review is to discuss the main characteristics of these very promising tools and to present the experimental and clinical results arguing for their unique tolerogenic ability.