Waid Thomas H, Thompson John S, Siemionow Maria, Brown Stephen A
Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA.
Drug Des Devel Ther. 2009 Sep 21;3:205-12. doi: 10.2147/dddt.s2750.
T10B9.1A-31/MEDI-500 is a nonmitogenic immunoglobulin M kappa murine monoclonal antibody (mAb) directed against the alpha-beta (alphabeta) heterodimer of the T-lymphocyte receptor complex. The hybridoma was first produced by fusing spleen cells from BALB/C mice immunized with human peripheral blood T-lymphocytes with SP2/O-Ag14 mutant myeloma cells. The mAb is produced and purified using multistep ion exchange and molecular sieve chromatography protocols. T10B9 has been used successfully to treat acute cellular rejection in renal transplantation and as an immunosuppression induction agent in heart and simultaneous kidney-pancreas transplantation. Because T10B9 is nonmitogenic and causes minimal cytokine release, both treatment of rejection and induction of immunosuppression were accomplished with significantly fewer and milder untoward effects (cytokine release syndrome) than its comparator OKT3. Since T10B9 is directed against the alphabeta heterodimer of the CD3 epitope, it spares the gamma delta (gammadelta) region. These gamma delta (gammadelta) T cells have a unique role in the immune response controlling many serious human diseases and perhaps facilitating the development of immunologic tolerance. T10B9 has a relatively short duration of action, depleting T cells for only 10 to 14 days, unlike the protracted depletion seen with thymoglobulin and Campath-1H. There is no B-lymphocyte depletion with T10B9 as there is with both of the aforementioned reagents. The lack of prolonged lymphocyte depletion may account for less infection observed with T10B9 treatment.
T10B9.1A-31/MEDI-500是一种非促有丝分裂的免疫球蛋白Mκ小鼠单克隆抗体(mAb),它靶向T淋巴细胞受体复合物的α-β(αβ)异二聚体。该杂交瘤最初是通过将用人外周血T淋巴细胞免疫的BALB/C小鼠的脾细胞与SP2/O-Ag14突变骨髓瘤细胞融合而产生的。该mAb通过多步离子交换和分子筛色谱法进行生产和纯化。T10B9已成功用于治疗肾移植中的急性细胞排斥反应,并作为心脏和同期肾胰腺移植中的免疫抑制诱导剂。由于T10B9不具有促有丝分裂作用且引起的细胞因子释放极少,与对照OKT3相比,其在治疗排斥反应和诱导免疫抑制时产生的不良影响(细胞因子释放综合征)明显更少且更轻微。由于T10B9靶向CD3表位的αβ异二聚体,因此它不会影响γδ区域。这些γδ T细胞在控制许多严重人类疾病的免疫反应中具有独特作用,并且可能有助于免疫耐受的发展。与胸腺球蛋白和Campath-1H所见的长期耗竭不同,T10B9的作用持续时间相对较短,仅使T细胞耗竭10至14天。与上述两种试剂不同,T10B9不会导致B淋巴细胞耗竭。T10B9治疗观察到的感染较少可能是由于缺乏长期的淋巴细胞耗竭。