Function of Bispecific Antibodies

Different formats can be constructed to:¹

• Direct protein-protein interactions by targeting different proteins on the same cell
• Activate cells by targeting two targets on different cell types

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Examples of Bispecific Formats

Dual-Variable-Domain Immunoglobulins (DVD-Ig)
A DVD-Ig combines the target-binding variable domains of two monoclonal antibodies, fused in tandem via naturally occurring or glycine-serine linkers to create a tetravalent, dual-targeting single agent.^2,3

• Bispecific and bivalent with regard to each antigen³
• Able to simultaneously bind antigens with all variable domains³
• Potentially allows less frequent administration³

Formats based on single-chain variable fragments (scFv)
ScFv-based bsAbs are fusions of only the variable regions of the heavy (VH) and light chains (VL) of immunoglobulins, connected with a short linker peptide.¹

• Exhibit high tumor specificity and tissue penetration.¹

Examples include:

• Tandem scFvs: Two scFvs are connected in a tandem orientation by a flexible linker that permits the antigen-binding sites to rotate freely.¹

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Therapeutic Potential

The versatility of bispecific antibodies introduces a wide range of potential applications.¹

bsAbs can be designed for multiple targeted approaches:¹

• Two epitopes on a single cancer target¹
• Two distinct antigens on the same tumor cell
• Two antigens on different cells within the tumor microenvironment

bsAbs can direct protein-protein interactions by targeting different proteins on the same cell.¹

• This allows for more efficient modification of cell signaling, potentially resulting in the deactivation of proliferation or inflammatory pathways.

They can also direct cell action in a specific setting by addressing two targets on different cell types.¹

• This allows for mediating the redirection of immune effector cells, such as NK cells and T cells, to tumor cells in order to potentially enhance tumor destruction.¹

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