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

这项研究旨在评估三种方法的有效性 抗Tac的各种形式，这是一种识别 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 受体不在静息细胞上表达，而在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。7只恒河猴中有5只收到 外毒素因中毒而死亡。接受Y-的三种动物之一 90在植入两周后还活着，没有其他 免疫抑制。对可能增强疗效的评估 在未修饰形式上的单克隆络合物以及 累积的毒性将与人类使用这种物质直接相关 器官移植和成人T-T治疗中的药物 细胞性白血病，一种表达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 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.