BsAbs Targeting Different Ligands

With years of experience, Creative Biolabs offers unrivaled bispecific antibodies (BsAbs) services. We help customers design, produce and characterize BsAbs that target different ligands and interfere with signaling.

In biology, a ligand is usually referred to a molecule that can produce a signal intercellular or intracellularly by binding to a target protein (receptor). The conformational change of the receptor results in further changes of cellular activities. Such ligand-receptor signaling networks integrate and distribute regulatory information and control programmed cell metabolism and programmed cell proliferation/ differentiation/ death. A healthy signaling network is essential for human health. Malfunctioning signaling pathways can lead to disorders while interfering with ligand-receptor signaling can be a strategy of disease treatment.

BsAbs Targeting Different Ligands

Many diseases involve multiple factors. These disease mediators/signaling pathways are often redundant or synergistic. Therefore, blockage of a single mediator or pathway many times cannot stop disease progression. BsAbs are capable of binding two different epitopes on two different antigens. This dual binding activity of BsAbs enables blockage of multiple pathological factors and pathways, which normally results in improved therapeutic efficacy. scFv-IgG, diabody, scFv-HSA fusion protein are some formats of BsAbs that have been developed to target soluble ligands in signaling pathways. Popular ligand targets include but not limit to growth factors, angiogenesis or vasculogenesis factors, and proinflammatory mediators. These factors are involved in cancer development, autoimmune disease, pulmonary and respiratory diseases, and vascular abnormalities in ophthalmology.

Figure 1. Schematic diagram of construction of the anti-αvβ6 diabody and the anti-αvβ6 cys-diabody. (White, J. B., 2015)

Examples of BsAbs Targeting Ligands

Ang-2, VEGF, IL-1a, IL-1b, IL-17A, IL-23 and IgE are some specific examples of the target ligands. It is reported that a BsAb can interfere with receptor ligands IL-1a and IL-1b; a bispecific sdAb binds the signaling ligands IL-17F and IL-17A; a scFv-Fc BsAb targets the IL17 and IL23 signaling. These factors block pro-inflammatory signaling pathways, reduce inflammatory reactions, and control disease progression and relieve syndromes. Another BsAb is reported to be able to treat idiopathic pulmonary fibrosis and other fibrotic indications by targeting IL4 and IL13 at the same time, which suppresses IL-4/IL-13-induced human fibroblast activation. A CrossMab molecule that recognizes Ang2 and VEGFA can reduce angiogenesis in wet age-related macular degeneration.

Figure 2. Structural characteristics and functional binding properties of CrossMAb RG7716. (Regula, J. T., 2016)

Creative Biolabs is a team unrivaled in expertise, stature, and credibility. We promise to provide customer one-stop, time- and budget-saving BsAb services. Our research team can develop various forms of bispecific antibodies targeting two ligands, which are potentially useful in scientific and clinical studies.

References

1. Kontermann R. E. Dual targeting strategies with bispecific antibodies. MAbs. 2012, 4(2): 182-197.
2. Regula, J.T.; et al. Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO molecular medicine. 2016, 8(11), 1265-1288.
3. White, J. B. Development and characterization of an α v β 6-specific diabody and a disulfide-stabilized α v β 6-specific cys-diabody. Nuclear medicine and biology, 2015, 42(12), 945-957.