RECRUIT-TandAb®
RECRUIT-TandAbs® specifically kill various tumor types by recruiting NK- or T-cells.
Highly suited for targeting tumor cells
Affimed´s original know-how of the activation process of cytotoxic immune cells, such as natural killer (NK) cells and cytotoxic T-cells, and the ability to isolate specific antibodies and generate novel antibody formats was crucial to the development of RECRUIT-TandAb®. A very strong and potent activator of natural killer cells is the CD16A receptor. The receptor is expressed as two isoforms: CD16A on NK-cells (with cytotoxic activity) and CD16B on granulocytes (with uncertain signaling function) that have more than 96% homology. Affimed was the only company to succeed in isolating a highly specific human antibody for the activation of the CD16A receptor.
Cytotoxic T-cells can be recruited via a similar mechanism of activation. Affimed generated a specific antibody against a subunit of the CD3 receptor, an essential part of the TCR complex.
Antibodies against CD16A and CD3 comprise the essential effector functions of the RECRUIT-TandAbs®. When combined with human antibodies directed against tumor targets, these tetravalent, bispecific RECRUIT-TandAbs® display a strong and efficient ADCC, thus resolving the issue of IgGs, which are often not sufficiently effective and need to be re-engineered.
This improved ADCC offers the opportunity to develop next generation antibodies based on clinically validated targets. Affimed is developing such candidates based on tetravalent bispecific antibodies targeting CD19 (AFM-11, AFM-12) and CD30 (AFM-13) for Lymphomas, or EpCAM (AFM-20) and EGFR (AFM-21) for solid tumors.
Besides cancer, the principle of the RECRUIT-TandAb® can be applied to further indications, such as infectious diseases in which Affimed pursues targets at the discovery level.
Mode of Action of TandAbs® recruiting NK-cells / T-cells
The TandAb® is used to crosslink the NK-cell or T-cell with the tumor cell. This crosslinking induces ADCC and the subsequent destruction of the tumor cell.
Affimed´s RECRUIT-TandAb® is able to strongly activate immune effector cells such as Natural Killer Cells (NK-cells) and T-cells. For the recruitment of NK-cells, Affimed has developed a highly specific and potent antibody against the FcyRIIIa (CD16A) receptor, and for the recruitment of T-cells, an antibody with high affinity against the CD3 receptor. The RECRUIT-TandAb® binds to a target cell molecule, e.g., CD30, with two of its binding sites, and to the CD16A receptor, with the other two binding sites. This cross-linking event initiates the killing activity of the respective NK-cell through antibody-dependent cell cytotoxicity (ADCC). Granules containing cell lysing components, such as perforin, granzyme and lysosomal enzymes, are transported towards the cell membrane of the NK-cell and subsequently secreted into the extracellular matrix. Perforin causes the formation of pores in the target cell, thereby facilitating the entry of the cell lysing components.
A very similar mode of action occurs when using T-cells as immune effector cells. CD3 is part of the T-cell receptor complex (TCR). If the TandAb® binds with its anti-CD3 binding sites to T-cells while simultaneously binding to a molecule on the surface of a tumor cell, the T-cells are activated to induce cell lysis of the targeted tumor cell (ADCC).
