This study, now in its fifth year, is 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 heterotopic 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. However, the animals died secondary to drug toxicity but with functioning grafts. Yttrium-90 chelation also caused significant prolongation of graft survival at moderate and low doses; however, high dose caused significant bone marrow suppression. Bone marrow suppression was averted by the addition of granulocyte colony stimulating factor. 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 antiTac. 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.
