A novel monoclonal antibody to CD40 prolongs islet allograft survival.
A novel monoclonal antibody to CD40 prolongs islet allograft survival.
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DOI：
10.1111/j.1600-6143.2012.04054.x
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Reimann KA
中科院分区：
文献类型：
--
作者：
Lowe M;Badell IR;Thompson P;Martin B;Leopardi F;Strobert E;Price AA;Abdulkerim HS;Wang R;Iwakoshi NN;Adams AB;Kirk AD;Larsen CP;Reimann KA
CD 40/CD 154共刺激通路阻断在免疫抑制策略中的重要性已得到充分证实。由于与针对CD 154的单克隆抗体相关的血栓栓塞并发症，目前的努力集中在对CD 40特异性的单克隆抗体上。在这里，我们提出了合理的发展和一种新的拮抗性单克隆抗体的特性CD 40。在用钥孔血蓝蛋白（KLH）免疫之前，用重组抗CD 40 mAb、2C 10或溶媒处理恒河猴。用2C 10处理成功地抑制了对KLH的T细胞依赖性抗体应答，而没有显著的外周B细胞耗竭。随后，MHC不匹配的猕猴进行门静脉内同种异体胰岛移植，并接受巴利昔单抗和西罗莫司与或不与2C 10。与接受单独的巴利昔单抗和西罗莫司的受体（移植物存活时间8、8、10天）相比，接受2C 10的受体（移植物存活时间304、296、265、163天）的胰岛移植物存活显著延长。通过用2C 10治疗所赋予的存活优势为阻断CD 40/CD 154途径在预防同种免疫应答中的重要性提供了进一步的证据。2C 10是一个特别有吸引力的候选翻译鉴于其有利的临床概况。
The importance of CD40/CD154 costimulatory pathway blockade in immunosuppression strategies is well documented. Efforts are currently focused on monoclonal antibodies specific for CD40 because of thromboembolic complications associated with monoclonal antibodies directed towards CD154. Here we present the rational development and characterization of a novel antagonistic monoclonal antibody to CD40. Rhesus macaques were treated with the recombinant anti-CD40 mAb, 2C10, or vehicle before immunization with keyhole limpet hemocyanin (KLH). Treatment with 2C10 successfully inhibited T cell-dependent antibody responses to KLH without significant peripheral B cell depletion. Subsequently, MHC-mismatched macaques underwent intraportal allogeneic islet transplantation and received basiliximab and sirolimus with or without 2C10. Islet graft survival was significantly prolonged in recipients receiving 2C10 (graft survival time 304, 296, 265, 163 days) compared to recipients receiving basiliximab and sirolimus alone (graft survival time 8, 8, 10 days). The survival advantage conferred by treatment with 2C10 provides further evidence for the importance of blockade of the CD40/CD154 pathway in preventing alloimmune responses. 2C10 is a particularly attractive candidate for translation given its favorable clinical profile.
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影响因子：
6.2
作者：
Kanmaz, T;Fechner, JH;Knechtle, SJ
通讯作者：
Knechtle, SJ
影响因子：
8.8
作者：
Vincenti, F.;Charpentier, B.;Larsen, C. P.
通讯作者：
Larsen, C. P.
DOI：
10.1111/j.1600-6143.2011.03736.x
发表时间：
2012-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Badell IR;Thompson PW;Turner AP;Russell MC;Avila JG;Cano JA;Robertson JM;Leopardi FV;Strobert EA;Iwakoshi NN;Reimann KA;Ford ML;Kirk AD;Larsen CP
通讯作者：
Larsen CP
影响因子：
56.9
作者：
Kolfschoten, Marijn van der Neut;Schuurman, Janine;Parren, Paul W. H. I.
通讯作者：
Parren, Paul W. H. I.
影响因子：
13.2
作者：
Porrini, Esteban;Delgado, Patricia;Torres, Armando
通讯作者：
Torres, Armando