POTENTIAL OF ANTI-INTERLEUKIN-2 RECEPTOR MONOCLONAL-ANTIBODIES IN SOLID-ORGAN TRANSPLANTATION

Monoclonal and polyclonal antibody preparations have been used for ind uction therapy after organ transplantation. Apart from serious adverse effects directly associated with their administration. for example th e cytokine release syndrome, the resulting profound and aspecific immu nosuppression leads to increased incidences of infections and, in the long term, of malignancies. To avoid the drawbacks of this aselective immunosuppression, monoclonal antibodies (mAbs) against specific T cel l activation determinants have been developed, In view of the pivotal role of interleukin-2 in the activation cascade of anti stimulated lym phocytes. mAbs directed against the interleukin-2 receptor (IL-2R) are believed to have a strong inhibitory effect only on activated T cells . The use of anti-IL-2R mAbs as prophylaxis against rejection after so lid organ transplantation is well tolerated and does not lead to an in creased incidence of infectious complications. The efficacy of these a gents in kidney transplantation has now been demonstrated in several s tudies, In liver transplantation, considerable differences have been r eported between the results obtained with different anti-IL-2R mAbs; i n the prophylaxis of rejection, inolimomab (BT-563) was the most effec tive agent, In human cardiac transplantation, inolimomab seems to be a s effective as muromonab-CD3 (OKT3) in preventing acute rejection, alt hough rejection episodes tend to occur a little earlier with inolimoma b, As shown by studies in kidney and liver transplantation. combinatio n of anti-IL-2R mAb with cyclosporin administered from the day of tran splantation appears to be the most effective strategy. Humanised anti- IL-2R mAbs are markedly less immunogenic and have improved pharmacokin etics, with prolonged terminal half-lives in vivo. Whether this leads to equal or improved efficacy and safety remains to be proven. The lon g half-life of humanised antibodies may potentially lead to prolonged coating of the IL-2R and over-immunosuppression.