TandAb® Technology
Affimed´s unique and proprietary TandAb® antibody platform is generating superior antibody therapeutics.
TandAb® Technology
TandAbs®, which were invented and developed by Affimed scientists, are tetravalent bispecific antibody formats that have two binding sites for each antigen. They bind to target molecules on the surface of, for example, tumor cells and can activate immune effector cells like cytotoxic T-cells or natural killer (NK) cells. TandAbs® possess the same avidity and affinity for each target as an IgG. Combined with their bispecificity, this format represents a unique and superior alternative to first generation antibody formats/scaffolds. In addition, TandAbs® have an excellent safety profile because they lack an Fc-portion. Production and downstream processing for TandAbs® have been established in eukaryotic cells and E.coli. The TandAb® molecules display excellent stability, making TandAb® antibodies a potent alternative to therapeutic monoclonal antibodies.
TandAb® Properties
- Enhanced target killing: antibody-dependent, cell-mediated cytotoxicity (ADCC)
- Excellent safety profile: lack of Fc-mediated side effects
- Same avidity as IgG: bivalent binding for each target
- Favorable half-life: better than other antibody scaffolds
- Production: can be expressed in E.coli and mammalian cells
- Robust GMP process: estabilished in mammalian cells
- Thermally stable: extrapolated shelf-life > 2 years
- No glycosylation: less problems regarding immunogenicity or product homogeneity
- Manifold applications: broad range of potential indications, such as oncology, inflammation, autoimmune diseases, asthma, COPD, ...
- Strong IP situation: patents granted for major world markets including EU, USA and Japan.
Superior Properties
The TandAb® molecules generated with Affimed´s proprietary technology platform have improved features compared to traditional IgGs and other antibody fragments.
TandAbs® are very specific and potent in target killing because of their enhanced ADCC. The exceptional killing potency was achieved using high affinity (dissociation constants lie in the sub-nanomolar range) and bivalent binding to one target, resulting in the same avidity as IgGs. Its better safety profile is due to the specific targeting of immune effector cells and to the lack of Fc-regions. TandAbs® are constructed solely of variable domains, therefore avoiding Fc-mediated severe side effects. They are fully functional without being glycosylated. On the one hand, this reduces the risk of potential immunogenicity and product homogeneity because of the different glycosylation patterns in eukaryotic production and, on the other, facilitates the upstream processing of TandAbs® in E.coli, giving it an attractive perspective regarding COGs.
Furthermore, the stability of TandAbs® to freezing and thawing has enabled the development of both frozen and lyophilised formulations. The TandAb® homodimers have a molecular weight of about 100 to 110 kDa, which is far above the renal threshold for the first-pass clearance. The estimated half-life of about two days is significantly better than other comparable formats based on antibody binding domains or alternative scaffolds.
Finally, because of their tetravalency, these molecules cover a very wide range of application possibilities, opening access to therapeutically important but difficult indications in the fields of oncology, inflammation and viral diseases. TandAbs® can act as a recruiting machinery (RECRUIT-TandAb®) for immune effector cells, e.g., T-cells or NK-cells, or as BiBLOCK-TandAbs® via the dual inhibition of two targets, e.g., signaling pathways.