Bivalent Llama Single-Domain Antibody Fragments against Tumor Necrosis Factor Have Picomolar Potencies due to Intramolecular Interactions

@inproceedings{Beirnaert2017BivalentLS,
  title={Bivalent Llama Single-Domain Antibody Fragments against Tumor Necrosis Factor Have Picomolar Potencies due to Intramolecular Interactions},
  author={Els Beirnaert and Aline Desmyter and Silvia Spinelli and Marc J. Lauwereys and Lucien A. Aarden and Torsten Dreier and Remy Loris and Karen Silence and Caroline Pollet and Christian Cambillau and Hans De Haard},
  booktitle={Front. Immunol.},
  year={2017}
}
The activity of tumor necrosis factor (TNF), a cytokine involved in inflammatory pathologies, can be inhibited by antibodies or trap molecules. Herein, llama-derived variable heavy-chain domains of heavy-chain antibody (VHH, also called Nanobodies™) were generated for the engineering of bivalent constructs, which antagonize the binding of TNF to its receptors with picomolar potencies. Three monomeric VHHs (VHH#1, VHH#2, and VHH#3) were characterized in detail and found to bind TNF with sub… CONTINUE READING

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