美国辛辛那提大学研究人员发现，一种癌症治疗药物同时也可以有效靶向产生移植排斥的免疫系统。Steve Woodle及其同事发现，一种通常用于治疗多发性骨髓瘤的癌症治疗药物硼替佐米（bortezomib）在治疗抗体导致的移植肾靶向排斥事件同样有效。该研究发表在12月27日Transplantation上。
B淋巴细胞，或B细胞，通过分泌攻击移植器官的抗体，在体液免疫系统中发挥主要作用。T淋巴细胞，或T细胞，则是通常认为导致移植器官免疫排斥的源头。研究人员表示，有大量文献证明硼替佐米在实验室试验中抑制移植排斥表现良好，而且在自身免疫疾病模型中也发挥作用。自2005 年以来，这项研究的研究人员开始研究靶向这些体液细胞的试剂。Steve Woodle 表示，这些体液细胞和其产生的抗体在免疫排斥中发挥的作用比此前想象的还要大，而靶向这些细胞的治疗药物开发已经滞后。当前治疗药物普遍不能靶向产生这些抗体的体液细胞。
研究人员对有器官移植排斥反应的6个接受肾移植的个体进行硼替佐米药物处理，评估和记录6个个体对该处理的反应。在每一个案例中，药物处理后迅速导致排斥反应的逆转，低水平抗体量时间延长，器官功能得到改善，排斥再次发作抑制作用至少维持5个月。
辛辛那提大学移植外科部癌症药理学家，论文共同作者Jason Everly 表示，与硼替佐米相关的毒性均可以预计、可控，同时与其他抗癌药物相比，硼替佐米毒性更低。然而，研究人员也表示，尽管数据鼓舞人心，很难估计这个药物的复杂性。当前，正在开展四项产业界支持的临床试验扩展这项研究。（生物谷Bioon.com）
生物谷推荐原始出处：
Transplantation. 86(12):1754-1761, December 27, 2008
Bortezomib Provides Effective Therapy for Antibody- and Cell-Mediated Acute Rejection.
Everly, Matthew J. 1; Everly, Jason J. 1; Susskind, Brian 2; Brailey, Paul 2; Arend, Lois J. 3; Alloway, Rita R. 4; Roy-Chaudhury, Prabir 4; Govil, Amit 4; Mogilishetty, Gautham 4; Rike, Adele H. 1; Cardi, Michael 5; Wadih, George 5; Tevar, Amit 1; Woodle, E Steve 1,6
Abstract:
Background. Current antihumoral therapies in transplantation and autoimmune disease do not target the mature antibody-producing plasma cell. Bortezomib is a first in class proteosomal inhibitor, that is Food and Drug Administration approved, for the treatment of plasma cell-derived tumors that is multiple myeloma. We report the first clinical experience with plasma cell-targeted therapy (bortezomib) as an antirejection strategy.
Methods. Eight episodes of mixed antibody-mediated rejection (AMR) and acute cellular rejection (ACR) in six transplant recipients were treated with bortezomib at labeled dosing. Monitoring included serial donor-specific antihuman leukocyte antigen antibody (DSA) levels and repeated allograft biopsies.
Results. Six kidney transplant patients received bortezomib for AMR and concomitant ACR. In each case, bortezomib therapy provided (1) prompt rejection reversal, (2) marked and prolonged reductions in DSA levels, (3) improved renal allograft function, and (4) suppression of recurrent rejection for at least 5 months. Moreover, immunodominant DSA (iDSA) (i.e., the antidonor human leukocyte antigen antibody with the highest levels) levels were decreased by more than 50% within 14 days and remained substantially suppressed for up to 5 months. One or more additional DSA were present at lower concentrations (non-iDSA) in each patient and were also reduced to nondetectable levels. Bortezomib-related toxicities (gastrointestinal toxicity, thrombocytopenia, and paresthesias) were all transient.
Conclusions. Bortezomib therapy: (1) provides effective treatment of AMR and ACR with minimal toxicity and (2) provides sustained reduction in iDSA and non-iDSA levels. Bortezomib represents the first effective antihumoral therapy with activity in humans that targets plasma cells.
