Kontermann R E, Wing M G, Winter G
MRC Centre for Protein Engineering, Cambridge, UK.
Nat Biotechnol. 1997 Jul;15(7):629-31. doi: 10.1038/nbt0797-629.
We describe the engineering of antibody fragments produced in bacteria for recruitment of complement effector functions. From a phage display repertoire we isolated human antibody fragments directed against complement C1q, and linked these to lysozyme-specific antibody fragments, creating bispecific antibodies (diabodies). One diabody was able to recruit C1q, resulting in efficient lysis of lysozyme-coated sheep erythrocytes, and also induced rosette-formation of erythrocytes with human monocytes and phagocytosis after phorbol ester stimulation. These diabodies may have therapeutic applications requiring the activation of complement.
我们描述了在细菌中产生的用于募集补体效应功能的抗体片段的工程化。从噬菌体展示文库中，我们分离出针对补体C1q的人源抗体片段，并将这些片段与溶菌酶特异性抗体片段相连，从而产生双特异性抗体（双体）。一种双体能够募集C1q，导致溶菌酶包被的绵羊红细胞有效裂解，并且在佛波酯刺激后还能诱导红细胞与人类单核细胞形成玫瑰花结以及吞噬作用。这些双体可能在需要激活补体的治疗应用中发挥作用。
