Creative Biolabs provides custom scFv4-IgG BsAb design and construction services for therapeutic antibody engineering study. Our innovative scientists have developed powerful technique and method to generate multispecific antibodies with satisfactory controllability and operability. We guarantee to offer the reliable and efficient services to meet our customer’s individual requirements.
Bispecific antibodies (BsAbs) have great potential for human applications and have exhibited promise in many small-scale clinical trials as cancer imaging and therapy agents. However, due to the insufficient of production methods, broad clinical evaluation of BsAbs has been blocked. In the past years, various recombinant approaches have been developed for the generation of bispecific and/or bivalent and multivalent antibody fragments. Bispecific and/or bivalency have been performed by fusing two single-chain Fv (scFv) or Fab by flexible linkers, CHCL-heterodimerization, leucine zipper and diabody format. The common strategy for generating BsAb-IgG contains chemical cross-linking of two different IgG molecules or co-expressing of two different IgGs in a hybrid hybridoma. Nevertheless, in both methods, purification of the BsAb-IgG from the non-functional species and non-cognate heavy-light chain pairs is usually different and the yield is general low.
Figure 1. Schematic diagram of the scFv4-IgG (Spiess, C., 2015).
Creative Biolabs has established a useful method for the generation of a novel IgG-like BsAb via the natural dimerization mechanism between IgG heavy and light chains. Two single-chain Fv (scFv) of different specificity are integrated to the first constant domain of human heavy chain (CH1) and the constant domain of humanκchain (CL), to produce two polypeptides, (scFv)1-CL and (scFv)2-CH1-CH2-CH3, respectively. Co-expression of the two polypeptides in mammalian cells leads to the production of a covalently linked IgG-like hetero-tetramer with dual specificity, named as scFv4-IgG. Our methods produce a homogeneous bispecific IgG-like antibody product, each of which processing four antigen binding sites, two for each of its target antigens. A scFv4-IgG was prepared through two scFv antibodies each directed against a different epitope of a vascular endothelial growth factor receptor.
According to bivalent binding of its target antigens, scFv4-IgGs exhibit several advantages. Firstly, the scFv4-IgG is able to simultaneously bind to the two epitopes on the receptor. Secondly, the scFv4-IgG maintains the antigen-binding efficacy and biological activity of its component antibodies. Secondly, bivalency of scFv4-IgG could improve binding avidity, which enables to compensate for the lower affinity of each individual component of the BsAb. Moreover, bivalent binding may lead to receptor cross-linking or dimerization which, in many cases, is essential to trigger biological responses.
With our well-established scFv4-IgG generation platform, the experienced scientists here at Creative Biolabs is dedicated to help you develop therapeutic BsAbs. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
1. Spiess, C.; et al. Alternative molecular formats and therapeutic applications for bispecific antibodies. Molecular immunology. 2015, 67(2): 95-106.
2. Zuo, Z.; et al. An efficient route to the production of an IgG-like bispecific antibody. Protein engineering. 2000, 13(5): 361-367.