Tribodies: Fab–scFv Fusion Proteins as a Platform to Create Multifunctional Pharmaceuticals

Chapter

Abstract

Tribodies are multifunctional recombinant antibody derivatives, which utilize the natural in vivo heterodimerization of the heavy chain (Fd fragment) and light chain (L) of a Fab fragment, to form a scaffold, upon which additional functions can be incorporated, such as additional binders – e.g., scFv binding domains.

Each chain can be extended preferably at the C terminus with an additional scFv binder. The chains are coproduced in mammalian cells, where the host-cell BiP chaperone drives the formation of the heavy chain–light chain heterodimer (Fd:L) – this reaction does not appear to be inhibited by the chain extensions, and leads to a very specific heterodimerization, using molecules abundantly present in serum (non-immunogenic)

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.

This design allows easy engineering of multispecificity in a single molecule, e.g., bispecific antibodies bivalent for the target and monovalent for effector activation (e.g., for T-cell activation), or trispecific antibodies pur sang.

Keywords

Bispecific Antibody Bivalent Binding scFv Molecule Antibody Derivative Monovalent Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Biotecnol SAOeiras (Lisbon)Portugal

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