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Potential of Anti-Interleukin-2 Receptor Monoclonal Antibodies in Solid Organ Transplantation

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Summary

Monoclonal and polyclonal antibody preparations have been used for induction therapy after organ transplantation. Apart from serious adverse effects directly associated with their administration, for example the cytokine release syndrome, the resulting profound and aspecific immunosuppression 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 cell activation determinants have been developed. In view of the pivotal role of interleukin-2 in the activation cascade of antigen-stimulated lymphocytes, 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 solid organ transplantation is well tolerated and does not lead to an increased incidence of infectious complications. The efficacy of these agents in kidney transplantation has now been demonstrated in several studies. In liver transplantation, considerable differences have been reported between the results obtained with different anti-IL-2R mAbs; in the prophylaxis of rejection, inolimomab (BT-563) was the most effective agent. In human cardiac transplantation, inolimomab seems to be as effective as muromonab-CD3 (OKT3) in preventing acute rejection, although rejection episodes tend to occur a little earlier with inolimomab. As shown by studies in kidney and liver transplantation, combination of anti-IL-2R mAb with cyclosporin administered from the day of transplantation appears to be the most effective strategy.

Humanised anti-IL-2R mAbs are markedly less immunogenic and have improved pharmacokinetics, with prolonged terminal half-lives in vivo. Whether this leads to equal or improved efficacy and safety remains to be proven. The long half-life of humanised antibodies may potentially lead to prolonged coating of the IL-2R and over-immunosuppression.

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  1. Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, Dr Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands

    Teun van Gelder & Willem Weimar

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van Gelder, T., Weimar, W. Potential of Anti-Interleukin-2 Receptor Monoclonal Antibodies in Solid Organ Transplantation. BioDrugs 8, 46–55 (1997). https://doi.org/10.2165/00063030-199708010-00006

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