MONOCLONAL-ANTIBODIES IN ORGAN-TRANSPLANTATION

Monoclonal antibody (mAb) technology has made possible the production of designer proteins, specifically reactive with almost any conceivabl e biological molecule. Using these reagents, the surface molecules on cells crucial for allograft rejection have been identified and describ ed in detail. These structures can now be selectively targeted by mAb- based therapy in order to prevent rejection. For instance, the CD3 mol ecule, expressed on all mature T lymphocytes, triggers T cell activati on, a key event in rejection. OKT3, an anti-CD3 mAb, disrupts T cell f unction and is now the agent of choice for the treatment of severe rej ection episodes. MAbs targeting other T cell molecules are currently b eing investigated. Some of the most promising, the anti-CD4, anti-ICAM -1, and anti-interleukin 2 receptor mAbs, have already induced donor-s pecific tolerance in rodent models. These hosts accept permanently a g enetically incompatible graft after only a limited period of mAb thera py. Interestingly, anti-ICAM-1 also diminishes the ischemic injury of preservation. The development of these new molecular agents, effective ly directed to specific cellular targets, will likely play an increasi ngly important role in future clinical protocols, and perhaps finally provide a means to achieve long-term tolerance in human allograft reci pients.