Once selected from the libraries, Affimed's single chain Fv antibodies can be converted into a variety of formats such as the proprietary TandAb and Flexibody formats, full length antibodies, Fabs and other fragments comprising only antibody variable domains. The choice of the format depends on the desired function of the antibody and the targeted clinical indication:
IgG antibodies
Full length antibodies are very useful for indications requiring a long half-life and/or Fc effector functions such as ADCC (antibody dependent cellular cytotoxicity) or CDC (complement dependent cytotoxicity).
Fabs
Fabs, being monovalent, are useful for blocking the activation of receptors since they are not able to cross-link with one another.
scFv and Diabodies
Antibodies with two different binding domains can be created either through the binding of two scFv with a simple peptide link (scFv2) or through the dimerisation of two monomers (Diabodies). Such bispecific antibodies are particularly useful for the recruitment of cytotoxic immune cells to lyse tumor cells.
TandAbs and Flexibodies
To increase their efficacy and usefulness as therapeutic agents, Affimed has developed proprietary tetravalent bispecific antibodies (TandAbs and Flexibodies) which have two binding sites for an activating receptor on immune effector cells such as cytotoxic T cells or natural killer cells and two binding sites for a target molecule on the surface of tumor cells.
TandAbs
In contrast to a bispecific Diabody, a bispecific TandAb is a homodimer consisting of only one polypeptide. Because the two different chains of a Diabody can build three different dimers only one of which is functional, it is simpler and cheaper to produce and purify this homogeneous product. Moreover, the TandAb shows better binding properties (possessing twice the number of binding sites) and increased stability in vivo.Another major advantage for therapeutic applications is its relatively large size compared to a Diabody or two linked scFv, since these smaller bivalent molecules are close to the size for first pass renal clearance and must be administered by continuous infusion in order to be effective. TandAbs have proved a highly efficient antibody format for recruiting cytotoxic T cells or natural killer cells and are especially suited to tumor-targeting. Affimed's lead products (AFM11, AFM12, AFM13) are all TandAbs.
Flexibodies
Flexibodies are a combination of scFv with a Diabody multimer motif resulting in a multivalent molecule with a high degree of flexibility for joining two molecules which are quite distant from each other on the cell surface. Experiments have confirmed this molecule's excellent binding properties, which has been patented by Affimed.
Affimed's proprietary antibody formats