Académie royale de Médecine de Belgique

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Dominique Latinne

(Séance du 28 octobre 2000)

TOLERANCE INDUCTION IN PRIMATES BY MONOCLONAL ANTIBODIES

par Dominique LATINNE (Laboratoire de Transplantation et d’Immunologie expérimentale – UCL). 

Several mABs directed against surface molecules involved in interaction between T cells and antigen presenting cells or target cells have been developed and tested in prevention or treatment of allograft rejection in experimental models or even in humans.  An anti-CD3 MAB, OKT3, was the first mAB used in transplantation followed by many others directed against different targets : CD25, CD52, CD2…

Recently, several experimental trials were conducted in primates using mAbs or fusion protein directed either against CD3 molecule or costimulatory signals as CD28/CTLA-4, CD2 or CD154 (CD40L) with promising results in order to attempt allograft tolerance.

Attractive associations combine mAbs directed against costimulatory molecules such as CD2, CD28, CD80, CD86, CD40 or CD154, as well as immune manipulation like chimerism induction by non myeloablative regimen.  The possibility to obtain a specific tolerance by blocking the secondary signals of activation, while preserving the first one could be tested.  A better knowledge of the mechanisms allowing to get a tolerance in adults where the immune repertoire is already mature is still necessary in order to reach this goal which seems clser than before.  

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