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BsAbs Targeting Different Epitopes

As a top leader in bispecific antibody (BsAb) engineering and production, Creative Biolabs offers a broad range of BsAbs. We can design and produce customized BsAbs targeting different epitopes, which may make a significant contribution to the development of therapeutics.

The antigen-binding site (also known as paratope) of an antibody recognizes and binds to an epitope (also known as antigenic determinant) of an antigen. BsAbs are capable of binding two different epitopes on one antigen or on two different antigens, which increases the functional affinity and neutralizing/activating potential of antibodies. Many diseases involve the redundant or synergistic action of disease mediators. BsAbs can target two of such mediators at the same time, block multiple pathological factors/ pathways, and improve therapeutic efficacy.

Schematic diagram of Dual targeting strategy with BsAb.

Figure 1. Schematic diagram of Dual targeting strategy with BsAb.

Generally, an epitope contains approximately five or six amino acid residues. Epitopes can be continuous (composed of a linear sequence of amino acids) or discontinuous (require a particular conformation/folding of the protein). The antigen-antibody interaction is a very important immune response and the epitope-paratope recognition is critical for this interaction. Capable of binding two different epitopes, BsAbs can be directed against different target molecules or against different epitopes of the same target, while the target molecules can be soluble ligands and/or cell-surface receptors.

Targeting Two Epitopes on the Same Target

Certain BsAbs are designed to work as potent antagonists as they can simultaneously bind to two epitopes on the same antigen. One example is that a bispecific diabody, which targets two different epitopes on the vascular endothelial growth factor receptor 2 (VEGFR2), efficiently blocks VEGF-VEGFR2 binding. Neither of the scFv fragments alone shows any inhibitory activity. This diabody thus works as a potent antagonist and inhibited VEGF-induced activation of the receptor and subsequent mitogenesis of endothelial cells.

Targeting Two Epitopes on Two Different Target Molecules

There are many redundant or synergistic disease mediators/signaling pathways. BsAbs can block two pathological factors/ pathways at the same time. Various formats of BsAbs (e.g., scFv-IgG, diabody, scFv-HAS fusion protein, and DART BsAb) have been developed to target soluble ligands and/or cell-surface receptors (e.g., VEGFR2, HER2). This strategy is widely used for treatment for cancer and diseases related to excessive/ unwanted inflammation. One example is the DVD-Ig ABT981 molecule. It interferes with the receptor ligands IL-1a and IL-1b and blocks subsequent pro-inflammatory pathways. It reduces inflammatory reactions and greatly relieves syndromes in rheumatoid arthritis. It is also known that by targeting different epitopes of virions, BsAbs can be used to target viruses. This is especially useful for viruses with high mutation rate and patients with infection of different virus strains. It has been reported that certain BsAbs have promising activities on HIV-1 envelope targeting or hepatitis B surface antigen targeting, and potent virus-neutralizing activities.

Different forms of BsAbs. (Stamova, S., 2012)

Figure 2. Different forms of BsAbs. (Stamova, S., 2012)

For years, Creative Biolabs has been dedicated to providing customers the best BsAb services. We have developed a brilliant and experienced BsAb research team, as well as advanced antibody engineering platforms. Our first-class technology and scientists will help customers develop various forms of bispecific antibodies for different purposes.

References

1. Dübel, S. Handbook of therapeutic antibodies (Vol. 1). John Wiley & Sons. 2013.
2. Stamova, S.; et al. Cancer immunotherapy by retargeting of immune effector cells via recombinant bispecific antibody constructs. Antibodies. 2012, 1(2): 172-198.

Our services and products are only for lab research, not for any diagnostic or therapeutic use.

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