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

使用单克隆抗 TAC 抗体作为心脏异种移植物的免疫抑制

• 批准号: 3942873
• 负责人: M M COOPER
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3942873
• 关键词: T lymphocyte; exotoxins; heart transplantation; immunoconjugates; immunosuppression; interleukin 2; monoclonal antibody; nonhuman therapy evaluation; xenotransplantation; yttrium

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.

本研究旨在评估三种方法的有效性。 形式的抗Tac，一种单克隆抗体， 白细胞介素-2（IL-2）受体作为唯一免疫抑制疗法 一种灵长类动物心脏异种异位移植模型。 的IL-2 受体不在静息细胞上表达，但在T细胞上表达。 与外来移植物相互作用激活的细胞 抗原 未结合抗Tac和螯合至 假单胞菌外毒素和90钇（Y-90），一种β发射 同位素的有效性和安全性进行评估。 移植物分析 存活、特定T细胞组成的改变 表型和毒性通过比较动物 未接受免疫抑制的患者（N=3）与接受 各种形式的抗Tac抗体（N=15）。 5只动物接受抗Tac 只是没能提高存活率 5/7恒河猴接受 外毒素中毒死亡。 三只接受Y- 90例患者在植入后两周存活良好， 免疫抑制 可能增强疗效的评价 的单克隆螯合物超过未修饰的形式，以及 累积的毒性将与人类使用这种药物直接相关， 在器官移植和治疗成人T- 细胞白血病，表达Tac抗原的白血病。