Creative Biolabs is an indubitable leader in antibody development and manufacture. Equipped with the most advanced antibody engineering platforms, scientists in Creative Biolabs can help customers design and produce suitable bispecific antibodies (BsAbs) based on the mode of action.
The rapid development of antibody engineering technologies (e.g., genetic engineering, chemical conjugation, and hybrid-hybridoma) in the past few decades greatly promotes the development of therapeutic BsAbs. The design of modern BsAbs normally is target-based, mode of action (MOA)-based, or application-based. Therapeutic BsAbs mainly function through four MOAs: immune cell recruitment, signaling interference, forced protein associations, and payload delivery.
Figure 1. Mode of action of BsAbs. (Kontermann, R. E., 2015)
T cells and Natural killer (NK) cells are important cytotoxic immune cells that have important roles in tumor prevention/ treatment. Specific BsAbs can retarget immune cells to tumor cells by binding tumor-associated antigens on tumor cells and CD3 on T cells or CD16 (FcγRIII)/CD56 on NK cells. The Fc region of certain BsAbs can also recruit accessory cells (e.g., macrophages and dendritic cells) by recognizing the Fcγ receptor (FcγR). Once immune cells are redirected to and make contacts with tumor cells, subsequent anti-tumor reactions (e.g., the release of cytokines and phagocytosis) eventually kill tumor cells. Therefore immune cell recruitment is a popular MOA of therapeutic BsAbs for cancer treatment.
The complex signaling network takes control of the integration and distribution of signals and regulatory information. Many disorders, including cancers and autoimmune diseases, involve malfunctioning signaling pathways. At the same time, receptor signaling interference in some cases control the development of certain disorders. Capable of interfering with two (or more) receptors or ligands simultaneously, BsAb reduces the possibility of escaping mechanisms and increases drug efficacy. A number of BsAbs have been designed to block ligand-receptor interactions involved in cell proliferation, cell motility, and angiogenic development, to control cancer progression. Therapeutic BsAbs have also been applied to ophthalmology, immunology, and pulmonary/ respiratory diseases. These BsAbs interfere with angiogenesis/vasculogenesis factors or pro-inflammatory signaling pathways.
Another MOA of BsAbs is forcing the associations of proteins. One well-known example in this category is the BsAb RG6013, anti-FIXa/FX. This KIH-common light chain IgG derivative is used in patients with the bleeding disorder hemophilia A. It mimics coagulation factor VIIIa, which is missing in hemophilia A patients, binds Factor IXa and Factor X simultaneously, and triggers subsequent pathways.
BsAbs can also be applied to payload (drugs, radiolabels or other small molecules) delivery. In pre-targeting settings, cold BsAb is first injected to localize the target cells. After a short time, free BsAbs are cleared from the blood and organs. Then the payload is injected and directed to target cells by BsAbs. BsAb-mediated payload delivery is widely used in radio-immunodetection and radio-immunotherapy, which greatly improves the specificity and sensitivity of imaging and therapeutic effects in cancer treatment.
There is a dramatic increase in the global sales and commercial interest of therapeutic monoclonal BsAbs in recent years. Creative Biolabs is experienced in design and production of various kinds of BsAbs. The top research team in Creative Biolabs can provide customers time- and budget-saving BsAb services.
1. Kontermann, R. E.; Brinkmann, U. Bispecific antibodies. Drug discovery today. 2015, 20(7): 838-847.
2. Zhukovsky, E. A.; et al. “Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection. Current opinion in immunology. 2016, 40: 24-35.