title: Comparison of newly developed anti-bone morphogenetic protein 4 llama-derived antibodies with commercially available BMP4 inhibitors.
abstract: Due to improved understanding of the role of bone morphogenetic protein 4 (BMP4) in an increasing number of diseases, the development of selective inhibitors of BMP4 is an attractive therapeutic option. The currently available BMP4 inhibitors are not suitable as therapeutics because of their low specificity and low effectiveness. Here, we compared newly generated anti-BMP4 llama-derived antibodies (VHHs) with 3 different types of commercially available BMP4 inhibitors, natural antagonists, small molecule BMPR inhibitors and conventional anti-BMP4 monoclonal antibodies. We found that the anti-BMP4 VHHs were as effective as the natural antagonist or small molecule inhibitors, but had higher specificity. We also showed that commercial anti-BMP4 antibodies were inferior in terms of both specificity and effectiveness. These findings might result from the fact that the VHHs C4C4 and C8C8 target a small region within the BMPR1 epitope of BMP4, whereas the commercial antibodies target other areas of the BMP4 molecule. Our results show that the newly developed anti-BMP4 VHHs are promising antibodies with better specificity and effectivity for inhibition of BMP4, making them an attractive tool for research and for therapeutic applications.
authors.affiliation: a Center for Experimental & Molecular Medicine , Academic Medical Center , Meibergdreef , Amsterdam , The Netherlands.
authors.forename: Silvia
authors.initials: S
authors.lastname: Calpe
authors.affiliation: a Center for Experimental & Molecular Medicine , Academic Medical Center , Meibergdreef , Amsterdam , The Netherlands.
authors.forename: Ana C P
authors.initials: AC
authors.lastname: Correia
authors.affiliation: a Center for Experimental & Molecular Medicine , Academic Medical Center , Meibergdreef , Amsterdam , The Netherlands.
authors.forename: Maria Del Carmen
authors.initials: Mdel C
authors.lastname: Sancho-Serra
authors.affiliation: a Center for Experimental & Molecular Medicine , Academic Medical Center , Meibergdreef , Amsterdam , The Netherlands.|b Department of Gastroenterology & Hepatology , Academic Medical Center , Meibergdreef, Amsterdam , The Netherlands.
authors.forename: Kausilia K
authors.initials: KK
authors.lastname: Krishnadath
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology*; D055415:Bone Morphogenetic Protein 4 / Q000037:antagonists & inhibitors* / Q000276:immunology; D002161:Camelids, New World / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D061905:Single-Domain Antibodies / Q000276:immunology*
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D061905:Single-Domain Antibodies
keywords: BMP inhibitors; BMP4; Noggin; VHH; llama antibodies