Interleukin 2 receptor-targeted therapy--rationale and applications in organ transplantation

Despite major advances in immunopharmacology for use in clinical organ transplantation, graft rejection and drug-induced side effects remain the major problems with currently available immunosuppressive modalities. Recent advances in hybridoma technology have produced relatively effective and reproducible biological immunosuppression with monoclonal antibodies; indeed, OKT3 and anti-T12 mAbs have been employed with considerable success as adjuncts to chemical suppression in treating rejection. Nonetheless, the use of such antibodies broadly reactive to differentiation antigens on T lymphocytes does not solve the problems of side effects caused by general immunosuppression. An ideal therapeutic agent should target only lymphocytes that participate in rejection of foreign tissue without affecting physiological host immune surveillance and normal defense mechanisms. Theoretically, this goal could be achieved by "antigenic suicide," or by using the appropriate antiidiotypic antibodies or mAbs against the antigen combining site of T cell receptors. However, because of the intense polymorphism of transplantation antigens and the vast genetic repertoire encoding for the T cell antigen receptor, success of such forms of specific immunosuppression, at least at this time, is highly improbable.