Department of Medicine, Division of Nephrology, Staten Island University Hospital, NY, USA.
Expert Rev Clin Immunol. 2012 Aug;8(6):527-36. doi: 10.1586/eci.12.42.
Full T-cell activation in alloimmunity requires the engagement of several costimulatory molecules. CTLA-4-Ig and its commercially available fusion proteins, belatacept and abatacept, are used to block CD80/86 and promote T-cell tolerance. Belatacept, a higher binding affinity molecule, is currently approved for clinical use in renal transplantation. The results of two Phase III clinical trials showed a similar patient/graft survival, with better renal function at a 3-year follow-up compared with conventional immunosuppression. There was a higher risk of early rejection and post-transplant lymphoproliferative disorder, especially with EBV-negative patients receiving kidneys from EBV-positive donors. Belatacept-treated groups had a better cardiovascular and metabolic profile. The authors review both preclinical and human studies of CTLA-4-Igs.
在同种异体免疫中，T 细胞的完全激活需要几种共刺激分子的参与。CTLA-4-Ig 及其商业上可获得的融合蛋白，贝利尤单抗和阿巴西普，被用于阻断 CD80/86 并促进 T 细胞耐受。贝利尤单抗是一种具有更高结合亲和力的分子，目前已被批准用于肾移植的临床应用。两项 III 期临床试验的结果表明，患者/移植物存活率相似，与传统免疫抑制相比，3 年随访时肾功能更好。早期排斥反应和移植后淋巴增殖性疾病的风险较高，尤其是 EBV 阴性患者接受 EBV 阳性供者的肾脏。贝利尤单抗治疗组具有更好的心血管和代谢特征。作者回顾了 CTLA-4-Ig 的临床前和人体研究。
