Generation of immunotoxins with super-targeting mAb in the acute myelocytic leukemia

我们构建了一个重组融合蛋白DT 3C，它包含了白喉毒素（DT）的催化和易位结构域以及链球菌G蛋白（3C）的三个IgG结合C结构域。MoAb的Fc与DT 3C结合，产生MoAb-DT 3C复合物（两个DT 3C分子与一个IgG分子缀合）。单克隆抗体-DT 3C复合物与抗原结合后，通过内化和转运进入细胞质，抑制DT蛋白质合成，产生胞质效应。通过使用这些，我们开发了一种独特的筛选系统，以建立癌症靶向抗原/抗体集。共获得224个单克隆抗体克隆，它们对白血病细胞进行免疫毒素细胞杀伤。我们的方法提供了一个很好的方式来获得有前途的上级单克隆抗体的抗体药物偶联（ADC）治疗。

We generated a recombinant fusion protein DT3C, which contained the catalytic and translocation domain of the truncated diphtheria toxin (DT) as well as the three IgG-binding C domains of streptococcal protein G (3C). Fc of MoAb binds with DT3C, resulting in a MoAb-DT3C complex (two DT3C molecules conjugated with one IgG molecule). The MoAb-DT3C complex binds with the surface Ag, being followed by internalization and translocation into the cytoplasm, leads to the cytocydal effect by protein synthesis inhibition of DT. By using these, we developed a unique screening system to establish cancer-targetable antigens/antibodies sets. In total 224 MoAb clones were obtained which performed immunotoxin cytocydal on leukemic cells. Our method provide an excellent way to obtain promising superior mAbs for antibodies drug conjugation(ADC) therapy.