This study is now in its fourth year to test the hypothesis that monoclonal antibody binding to IL-2 receptors on activated T-cells will influence graft survival especially when chelated to toxins or radioactive substances. Anti-Tac, a mouse derived monoclonal antibody to human IL-2 receptors has been used alone, with a modified pseudomonas exotoxin and to a beta emitter Yttrium-90 in allograft orthotopic subhuman cardiac transplants. The data show that Anti-Tac prolongs graft survival. Chelation to a pseudomonas exotoxin PE40 caused increased graft rejection and chelation to PE66 a modified pseudomonas exotoxin significantly prolonged graft survival, but the animals died with functioning grafts secondary to drug toxicity. Yttrium-90 chelation also caused significant prolongation of graft survival at moderate and low doses, however high dose caused significant bone marrow suppression. This graft survival was shown to be independent of radiation. A new modified (humanized) form of Anti-Tac has been developed and caused significant prolongation of graft survival over regular Anti-Tac. This humanized form has been made with recombinant DNA techniques and contains human constant regions and only the variable regions are of mouse origin. This is hypothesized to be less immunogenic.
