USE OF MONOCLONAL ANTI-TAC ANTIBODY AS IMMUNOSUPPRESSION FOR CARDIAC XENOGRAFTS

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This study is designed to evaluate the effectiveness of three forms of anti- Tac, a monoclonal antibody that recognizes the interleukin-2 (IL-2) receptor as sole immunosuppressive therapy in a model of heterotopic primate cardiac xenografting. The IL-2 receptor is nor expressed on resting cells but is expressed on T- cells activated by interaction with foreign transplantation antigens. Unconjugated anti-TAC and anti-Tac chelated to pseudomonal exotoxin and to 90 Yttrium (Y-90), a beta emitting isotope, are evaluated for efficacy and safety. Analysis of graft survival, modification of the composition of specific T-cell phenotypes, and toxicity were performed by comparing animals receiving no immunosuppression (n=3) with those receiving the various forms of anti-Tac (N=15). Five animals receiving anti-Tac only failed to have increased survival. Five of seven Rhesus receiving the exotoxin died of toxicity. Five animals received adequate doses of 90Y x-Tac for 14 days in total doses of 16-20 miCu with a prolongation of graft survival of 38 plus/minus 5 days. The evaluation of possible enhanced efficacy of the monoclonal chelates over the unmodified form as well as toxicity accrued will have direct relevance to human use of such agents in organ transplantation and in the treatment of adult T-cell leukemia, a leukemia expressing the Tac antigen.