Holliger P, Wing M, Pound J D, Bohlen H, Winter G
MRC Centre for Protein Engineering, Cambridge, UK.
Nat Biotechnol. 1997 Jul;15(7):632-6. doi: 10.1038/nbt0797-632.
Monospecific antibody fragments produced in bacteria lack the Fc portion of antibodies, and are therefore unable to recruit natural effector functions. We describe the use of a bispecific antibody fragment (diabody) to recruit the whole spectrum of antibody effector functions by retargeting serum immunoglobulin (Ig). One arm of the diabody was directed against the target antigen, and the other against the serum Ig. The bispecific diabodies were able to recruit complement, induce mononuclear phagocyte respiratory burst and phagocytosis, and promote synergistic cytotoxicity towards colon carcinoma cells in conjunction with CD8+ T-cells. Further, by virtue of binding to serum Ig their half-life (beta-phase) was increased fivefold compared to a control diabody of the same molecular weight. Such bispecific diabodies may provide an attractive alternative to monoclonal antibodies for serotherapy.
在细菌中产生的单特异性抗体片段缺乏抗体的Fc部分，因此无法募集天然效应功能。我们描述了使用双特异性抗体片段（双体）通过重新靶向血清免疫球蛋白（Ig）来募集整个抗体效应功能谱。双体的一个臂针对靶抗原，另一个臂针对血清Ig。双特异性双体能够募集补体，诱导单核吞噬细胞呼吸爆发和吞噬作用，并与CD8 + T细胞协同促进对结肠癌细胞的细胞毒性。此外，由于与血清Ig结合，其半衰期（β期）比相同分子量的对照双体增加了五倍。这种双特异性双体可能为血清疗法提供一种有吸引力的单克隆抗体替代物。
