Since the concept of bispecific antibodies was first proposed in 1960, with the rapid development of genetically engineered antibodies, immunology, and other related fields, the conceptual construction of bispecific antibodies, technological platforms, and product development have also evolved and innovated. Although anti-peptide/protein antibodies, anti-cell-based target antibodies, and anti-epitope antibodies have all played an important role in the field of biomedicine. However, bispecific antibodies, which are artificial antibodies that can specifically bind two antigens or antigenic epitopes at the same time, continue to be a hot research topic in the field of antibody engineering due to their specificity and bifunctionality. Bispecific antibodies play an important role in the treatment of tumors, autoimmune diseases, and other diseases. Based on our rich field experience and advanced research platform, Creative Biolabs provides comprehensive services to support premade antibody library screening and bifunctional antibody discovery.

Bifunctional Antibodies

A bifunctional antibody is also known as a bispecific antibody. Bispecific antibodies do not exist under natural conditions. It is achieved by cell fusion or recombinant DNA technology preparation. There are three commonly used methods for the preparation of bispecific antibodies, namely, the chemical cross-linking method, the hybridoma binding method, and the gene cloning method. The principle of the chemical cross-linking method is to form disulfide bonds between antibody molecules of different specificities, or F(ab'), through the action of specific chemical cross-linking agents, so as to produce heterodimers. The bispecific antibodies prepared by this method can directly utilize existing antibodies and have high yields, but their activity may be affected by damage to the antigen-binding site. The hybridoma conjugation method is based on conventional monoclonal antibody technology, in which hybridoma cells secreting two antibodies are fused to produce hybridomas that stably secrete bispecific antibodies. Co-expression of the respective immunoglobulin (Ig) genes produces two H and L chains, which combine to form a bispecific antibody with the characteristics of the parental Ig. Bispecific antibodies prepared by the hybridoma method are more random and less efficient, but they have better biological activity and a more stable antibody structure. Bispecific antibodies prepared by the gene cloning method can directly utilize existing antibodies and have a high yield, but their activity may be affected by damaging the antigen binding site.

Bispecific antibodies can target multiple antigens or epitopes and exert synergistic effects, which has more advantages than monoclonal antibodies. There are three main mechanisms of bispecific antibodies, including mediating immune cell killing, blocking dual-target signaling, and promoting the formation of functional complexes. Bispecific antibodies can be mediated by a variety of specific biological effects. For example, by bridging immune cells and tumor cells, the double specificity antibodies can recruit and activate the immune cells to kill tumor cells. Bispecific antibodies can inhibit or stimulate multiple signaling pathways and have a coordination effect. In addition, bispecific antibodies can mediate the formation of protein complexes and exert biological effects with the help of their bivalent structure.

However, there are many difficulties in the development of bispecific antibodies. Firstly, structural design, that is, how to effectively combine two different antigen recognition sites while improving the target antibody homogeneity and yield of the bispecific antibody to carry out a reasonable structural design. Secondly, to establish a suitable preclinical evaluation model, conventional animal models do not have target binding characteristics comparable to those of humans, such as that the expression of the target is not the same as that of human beings, the binding ability is different, the pharmacological effect is different, and the upstream and downstream signals of humanized animal models are different from those of human beings, which leads to difficulties in the preclinical evaluation model to correctly evaluate the reasonableness of the target design, the pharmacological effect, and the toxicological effect, and increases the difficulty in evaluating the reasonableness of the target design. This increases the difficulty of evaluating the rationality of the target design. Finally, the preparation technology platform needs to be continuously explored and optimized to develop a platform technology that combines drug ability, production feasibility, and scalability, and at the same time, the universality of the production platform should also be taken into consideration.

Creative Biolabs has a wealth of knowledge and experience in functional human antibodies. We would be happy to share with you our knowledge and experience in premade phage displayed human antibody library construction and bifunctional antibody discovery.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.