Improved stability of multivalent antibodies containing the human collagen XV trimerization domain |
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| Authors: | ángel M Cuesta David Sánchez-Martín Ana Blanco-Toribio Maider Villate Kelly Enciso-álvarez Ana Alvarez-Cienfuegos Noelia Sainz-Pastor Laura Sanz Francisco J Blanco Luis álvarez-Vallina |
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| Affiliation: | 1.Molecular Immunology Unit; Hospital Universitario Puerta de Hierro; Madrid, Spain;2.Leadartis S.L., Ferraz 3; Madrid, Spain;3.Structural Biology Unit; CIC bioGUNE; Parque Tecnológico de Bizkaia; Derio, Spain;4.IKERBASQUE; Basque Foundation for Science; Bilbao, Spain |
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| Abstract: | We recently described the in vitro and in vivo properties of an engineered homotrimeric antibody made by fusing the N-terminal trimerization region of collagen XVIII NC1 domain to the C-terminus of a scFv fragment [trimerbody (scFv-NC1)3; 110 kDa]. Here, we demonstrated the utility of the N-terminal trimerization region of collagen XV NC1 domain in the engineering of trivalent antibodies. We constructed several scFv-based trimerbodies containing the human type XV trimerization domain and demonstrated that all the purified trimerbodies were trimeric in solution and exhibited excellent antigen binding capacity. Importantly, type XV trimerbodies demonstrated substantially greater thermal and serum stability and resistance to protease digestion than type XVIII trimerbodies. In summary, the small size, high expression level, solubility and stability of the trimerization domain of type XV collagen make it the ideal choice for engineering homotrimeric antibodies for cancer detection and therapy.Key words: antibody engineering, multivalent antibody, collagen XVIII, collagen XV, tumor targeting |
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