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

本研究旨在评估三种形式的有效性。 抗Tac的一种单抗，它识别 白细胞介素2受体作为唯一的免疫抑制治疗 异位灵长类心脏移植模型的建立。白介素2 受体在静息细胞上也不表达，但在T细胞上表达 与异体移植相互作用激活的细胞 抗原。非偶联抗TAC和螯合抗TAC 假单胞菌外毒素和~(90)Y(Y-90)，aβ发射 对其有效性和安全性进行评估。关于嫁接的分析 存活，改变特定T细胞的组成 通过比较动物的表型和毒性 未接受免疫抑制的患者(n=3) 各种形式的抗他汀类药物(n=15)。五只动物接受反击 只是没能提高存活率。七只恒河猴中的五只 接受外毒素的人因中毒而死亡。收到五只动物 足够剂量的90Yx-Tac，共14天，总剂量16-20 MICU，移植物存活时间延长38加/减5天。 单抗可能增强疗效的评价 未经修饰的形式上的螯合物以及累积的毒性 与人类在器官中使用这类制剂有直接关系 在成人T细胞白血病的移植和治疗中， 表达Tac抗原的白血病。

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.