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Artículo

Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo

Fumey, William; Koenigsdorf, Julia; Kunick, Valentin; Menzel, Stephan; Schütze, Kerstin; Unger, Mandy; Schriewer, Levin; Haag, Friedrich; Adam, Gerhard; Oberle, Anna; Binder, Mascha; Fliegert, Ralf; Guse, Andreas; Zhao, Yong Juan; Lee, Hon Cheung; Malavasi, Fabio; Goldbaum, Fernando AlbertoIcon ; Van Hegelsom, Rob; Stortelers, Catelijne; Bannas, Peter; Koch Nolte, Friedrich
Fecha de publicación: 12/2017
Editorial: Nature Publishing Group
Revista: Scientific Reports
ISSN: 2045-2322
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Biotecnologías de la Salud

Resumen

The cell surface ecto-enzyme CD38 is a promising target antigen for the treatment of hematological malignancies, as illustrated by the recent approval of daratumumab for the treatment of multiple myeloma. Our aim was to evaluate the potential of CD38-specific nanobodies as novel diagnostics for hematological malignancies. We successfully identified 22 CD38-specific nanobody families using phage display technology from immunized llamas. Crossblockade analyses and in-tandem epitope binning revealed that the nanobodies recognize three different non-overlapping epitopes, with four nanobody families binding complementary to daratumumab. Three nanobody families inhibit the enzymatic activity of CD38 in vitro, while two others were found to act as enhancers. In vivo, fluorochrome-conjugated CD38 nanobodies efficiently reach CD38 expressing tumors in a rodent model within 2 hours after intravenous injection, thereby allowing for convenient same day in vivo tumor imaging. These nanobodies represent highly specific tools for modulating the enzymatic activity of CD38 and for diagnostic monitoring CD38-expressing tumors.
Palabras clave: Nanobodies , Cd38 , Imaging , Neutralizing Antibodies
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/53932
DOI: https://dx.doi.org/10.1038/s41598-017-14112-6
URL: https://www.nature.com/articles/s41598-017-14112-6
Colecciones
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Citación
Fumey, William; Koenigsdorf, Julia; Kunick, Valentin; Menzel, Stephan; Schütze, Kerstin; et al.; Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo; Nature Publishing Group; Scientific Reports; 7; 1; 12-2017
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