LeadArtis discloses a new strategy for making multispecific antibodies with controlled antigen binding domain orientation in the prestigious journal Scientific Reports (Nature publishing group).


In collaboration with prominent academic institutions (Aarhus University, CIC bioGUNE, Parc de Recerca Biomèdica and Molecular Immunology Unit, Hospital Universitario Puerta de Hierro), LeadArtis´scientists have developed a new approach to generate mono and multispecific antibodies by fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the human collagen XVIII trimerization domain (TIEXVIII). Further, rational design of multispecific single polypeptide “tandem” trimerbodies with defined stoichiometry and controlled orientation of the binding domains were generated by connecting two glycine-serine-based linkers to three VHH-TIEXVIII modules. Tandem trimerbody technology allows the generation of mono and multispecific VHH-based trimerbodies that are efficiently expressed in mammalian cells and display good biophysical properties. Importantly, trispecific VHH-based trimerbodies are capable of simultaneously binding to three distinctive antigens. Tandem trimerbodies may have applications for the dual targeting of two receptors for cancer therapy, the design of improved multiparatopic molecules, and the development of immune recruitment strategies.

The paper is online. Please visit (http://www.nature.com/articles/srep28643).

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