RECRUIT-TandAbs® specifically kill various tumor types by recruiting NK- or T-cells.
Highly suited for targeting tumor cells
Antibodies against CD16A (engaging NK-cells) and CD3 (engaging T-cells) 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 tumor cell killing, thus resolving the issue of IgGs, which are often not sufficiently effective.
This improved tumor cell killing offers the opportunity to develop next generation antibodies based on clinically validated and novel targets. Affimed is developing TandAbs® targeting CD19 (AFM-11) and CD30 (AFM-13) for the treatment of lymphomas, or further TandAbs® for the treatment of solid tumors.
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.
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 recruit 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 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. 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.