Therapeutic Potential
The versatility of bispecific antibodies introduces a wide range of potential applications.1
- bsAbs can be designed for multiple targeted approaches1:
- Two epitopes on a single cancer target
- 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
Novel Formats
Dual-Variable-Domain Immunoglobulins (DVD-IgTM)
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 penetration1
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; bispecific T cell engagers (BiTEs®) are based on this format.1
- Dual-affinity retargeting molecules (DARTs): VH of the first variable region is linked to the VL on a second chain, and the VH of the second variable region is linked to the VL on the first chain; an inter-chain disulfide bond stabilizes the DART.1