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

本研究旨在评估三种方法的有效性

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 not 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 7 Rhesus receiving the exotoxin died of toxicity. One of three animals receiving Y- 90 was alive and well two weeks after implant with no other immunosuppression. 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.