Nachreiner Thomas, Kampmeier Florian, Thepen Theo, Fischer Rainer, Barth Stefan, Stöcker Michael
Fraunhofer IME, Department of Pharmaceutical Product Development, Forckenbeckstr. 6, D-52074 Aachen, Germany.
J Neuroimmunol. 2008 Mar;195(1-2):28-35. doi: 10.1016/j.jneuroim.2008.01.001. Epub 2008 Feb 15.
We report the construction of a fusion protein comprising the extracellular domain of myelin oligodendrocyte glycoprotein (MOG) and a truncated version of Pseudomonas aeruginosa exotoxin A (ETA'). The chimeric immunotoxin targeted MOG-reactive B-lymphocytes by binding selectively to the appropriate receptors, leading to internalization and apoptosis of the target cells. The functionality of the immunotoxin was tested on a MOG-sensitive murine hybridoma cell line and ex vivo on freshly isolated splenocytes from transgenic IgH(MOG) mice. These data demonstrate, for the first time, the specific cytotoxicity of a MOG-containing recombinant immunotoxin expressed in bacteria towards MOG-reactive B-lymphocytes.
我们报道了一种融合蛋白的构建，该融合蛋白包含髓鞘少突胶质细胞糖蛋白（MOG）的细胞外结构域和铜绿假单胞菌外毒素A（ETA'）的截短形式。这种嵌合免疫毒素通过选择性地结合适当的受体靶向MOG反应性B淋巴细胞，导致靶细胞内化和凋亡。在MOG敏感的小鼠杂交瘤细胞系上以及在来自转基因IgH(MOG)小鼠的新鲜分离脾细胞上对免疫毒素的功能进行了体外测试。这些数据首次证明了在细菌中表达的含MOG重组免疫毒素对MOG反应性B淋巴细胞具有特异性细胞毒性。
