The Kidney Transplant Program of the University of Chicago as one of at least six Transplant Study Units in the NIAID's proposed Cooperative Clinical Trials in Transplantation will focus its suggestions for clinical trials on immunomodulation of transplant rejection via monoclonal antibodies against the recipient's T-cells. The broad long term objective is to provide immunosuppression that will sustain more than 80% of cadaver kidneys beyond five years after transplantation. At present not more than 50-60% of grafts function beyond five years. To accomplish this end we will propose clinical trials with new anti T-cell mAbs not previously tested in man in an effort to achieve more complete suppression of allorecognition in the perioperative period (including memory T-cells and B-cell responses to the donor) without triggering concomitant non specific T-cell activation and lymphokine production. It is likely that this can be achieved by new anti-CD3 mAbs that are minimally mitogenic and produce limited lymphokines. Monoclonal antibodies against CD3 and CD4 will be used singly and in combination for treatment of human subject. After less toxic but more effective induction immunosuppression has been achieved it is possible that treatment with highly selected populations of cells from the donor's bone marrow will confer added specificity to long-term immunosuppression with less dependence on long-term drug treatment.
