Tribodies are multifunctional recombinant antibody derivatives. The Fab fragment serves as a specific heterodimerization signal, and the two scFv fragments are each fused to a different Fab chain. In this way we obtain a molecule of intermediate molecular weight (100 kDa) which allows incorporating three different antibody fragments (Fig. 1). This manifold, tribody, can be used to create trivalent molecules as well as bispecific molecules with bivalent binding to only one target, as trispecific molecules. These heterodimers are stable, with each of the binders retaining their specific affinities, with the bivalent tribody having higher affinity, and higher activation of T-cell proliferation and cytotoxicity in vivo. The molecule also has more favorable properties for toxic payload delivery. It can be argued that delivering a T-cell activating activity can be regarded as a toxic function. Antibodies with such a function remaining in the body for a longer time have the potency to accumulate aspecifically or form deposits in healthy tissue.
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