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
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
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