New generation CD3 monoclonal antibodies: are we ready to have them back in clinical transplantation?
OBJECTIVE
The continuing problem of late graft loss and immunosuppressive drug toxicity forces us to explore new treatments for the induction of transplant tolerance. Monoclonal antibodies targeting molecules implicated in lymphocyte activation, in particular CD3/TCR, constitute a promising strategy.


RESULTS
Promising results were obtained from the use of antibodies targeting CD3/TCR, coreceptors or costimulatory pathways as tolerance-promoting tools in experimental transplantation. These antibodies do not uniformly depress the immune system but act in an antigen-specific manner by preferentially targeting effector T cells while preserving regulatory T cells. However, translation to the clinic proved to be more difficult than expected. New generation CD3 antibodies, currently used in phase II/III trials in autoimmunity, constitute a promising approach as, beside their immunosuppressive effect, they also express potent tolerogenic capacities. Importantly, CD3 therapy is effective especially when applied in primed hosts, highlighting the importance of the therapeutic window for tolerance induction.


CONCLUSIONS
Further investigations are required for adapting to the clinic monoclonal antibodies as substitutes for current immunosuppression. Our aim is to show that development of new therapeutic strategies/molecules may come from transversal-type research, in particular from experience in autoimmunity, as immune responses leading to autoimmunity and graft rejection involve similar pathways.
You
Sylvaine
S
aUniversité Paris Descartes, France bINSERM, Unité 1013, Paris, France *Sylvaine You and Lucienne Chatenoud contribute equally to the writing of this article.
Chatenoud
Lucienne
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015551:Autoimmunity / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016377:Organ Transplantation
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D061025:Costimulatory and Inhibitory T-Cell Receptors; D007166:Immunosuppressive Agents