美國(guó)辛辛那提大學(xué)研究人員發(fā)現(xiàn),，一種癌癥治療藥物同時(shí)也可以有效靶向產(chǎn)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(dǎo)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(xì)胞，或B細(xì)胞,，通過(guò)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(xì)胞,，或T細(xì)胞,，則是通常認(rèn)為導(dǎo)致移植器官免疫排斥的源頭。研究人員表示,，有大量文獻(xiàn)證明硼替佐米在實(shí)驗(yàn)室試驗(yàn)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(lái),，這項(xiàng)研究的研究人員開(kāi)始研究靶向這些體液細(xì)胞的試劑。Steve Woodle 表示,，這些體液細(xì)胞和其產(chǎn)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(xì)胞的治療藥物開(kāi)發(fā)已經(jīng)滯后,。當(dāng)前治療藥物普遍不能靶向產(chǎn)生這些抗體的體液細(xì)胞。
研究人員對(duì)有器官移植排斥反應(yīng)的6個(gè)接受腎移植的個(gè)體進(jìn)行硼替佐米藥物處理,，評(píng)估和記錄6個(gè)個(gè)體對(duì)該處理的反應(yīng)。在每一個(gè)案例中,，藥物處理后迅速導(dǎo)致排斥反應(yīng)的逆轉(zhuǎn),，低水平抗體量時(shí)間延長(zhǎng)，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(gè)月,。
辛辛那提大學(xué)移植外科部癌癥藥理學(xué)家，論文共同作者Jason Everly 表示,，與硼替佐米相關(guān)的毒性均可以預(yù)計(jì),、可控，同時(shí)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(jì)這個(gè)藥物的復(fù)雜性,。當(dāng)前，正在開(kāi)展四項(xiàng)產(chǎn)業(yè)界支持的臨床試驗(yàn)擴(kuò)展這項(xiàng)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.
