美國辛辛那提大學研究人員發(fā)現(xiàn),，一種癌癥治療藥物同時也可以有效靶向產生移植排斥的免疫系統(tǒng),。Steve Woodle及其同事發(fā)現(xiàn)，一種通常用于治療多發(fā)性骨髓瘤的癌癥治療藥物硼替佐米（bortezomib）在治療抗體導致的移植腎靶向排斥事件同樣有效,。該研究發(fā)表在12月27日Transplantation上,。
B淋巴細胞，或B細胞,，通過分泌攻擊移植器官的抗體,，在體液免疫系統(tǒng)中發(fā)揮主要作用。T淋巴細胞,，或T細胞,，則是通常認為導致移植器官免疫排斥的源頭。研究人員表示,，有大量文獻證明硼替佐米在實驗室試驗中抑制移植排斥表現(xiàn)良好,，而且在自身免疫疾病模型中也發(fā)揮作用。自2005 年以來,，這項研究的研究人員開始研究靶向這些體液細胞的試劑,。Steve Woodle 表示,，這些體液細胞和其產生的抗體在免疫排斥中發(fā)揮的作用比此前想象的還要大，而靶向這些細胞的治療藥物開發(fā)已經滯后,。當前治療藥物普遍不能靶向產生這些抗體的體液細胞,。
研究人員對有器官移植排斥反應的6個接受腎移植的個體進行硼替佐米藥物處理，評估和記錄6個個體對該處理的反應,。在每一個案例中,，藥物處理后迅速導致排斥反應的逆轉，低水平抗體量時間延長,，器官功能得到改善,，排斥再次發(fā)作抑制作用至少維持5個月。
辛辛那提大學移植外科部癌癥藥理學家,，論文共同作者Jason Everly 表示,，與硼替佐米相關的毒性均可以預計、可控,，同時與其他抗癌藥物相比,，硼替佐米毒性更低。然而,，研究人員也表示,，盡管數(shù)據(jù)鼓舞人心，很難估計這個藥物的復雜性,。當前,，正在開展四項產業(yè)界支持的臨床試驗擴展這項研究。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
