An efficient route to human bispecific IgG

作者：Merchant AM; Zhu ZP; Yuan JQ; Goddard A; Adams CW; Presta LG; Carter P^*

来源：Nature Biotechnology, 1998, 16(7): 677-681.

DOI：10.1038/nbt0798-677

• applied immunology
• antibody engineering
• phage display

Production of bispecific IgG (BsIgG) by coexpressing two different antibodies is inefficient due to unwanted pairings of the component heavy and light chains. To overcome this problem, heavy chains were remodeled for heterodimerization using engineered disulfide bonds in combination with previously identified "knobs-into-holes" mutations. One of the variants, S354C:T366W/Y349'C:T366'S:L368'A:Y407'V, gave near quantitative (similar to 95%) heterodimerization, Light chain mispairing was circumvented by using an identical light chain for each arm of the BsIgG, Antibodies with identical light chains that bind to different antigens were identified from an scFv phage library with a very restricted light chain repertoire for the majority (50/55) of antigen pairs tested, A BsIgG capable of simultaneously binding to the human receptors HER3 and cMpI was prepared by coexpressing the common light chain and corresponding remodeled heavy chains followed by protein A chromatography. The engineered heavy chains retain their ability to support antibody-dependent cell-mediated cytotoxicity as demonstrated with an anti-HER2 antibody.

• 出版日期1998-7