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

Autores
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 Alberto; Van Hegelsom, Rob; Stortelers, Catelijne; Bannas, Peter; Koch Nolte, Friedrich
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Fumey, William. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Koenigsdorf, Julia. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Kunick, Valentin. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Menzel, Stephan. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Schütze, Kerstin. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Unger, Mandy. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Schriewer, Levin. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Haag, Friedrich. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Adam, Gerhard. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Oberle, Anna. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Binder, Mascha. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Fliegert, Ralf. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Guse, Andreas. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Zhao, Yong Juan. Peking University; China
Fil: Lee, Hon Cheung. Peking University; China
Fil: Malavasi, Fabio. Università di Torino; Italia
Fil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina
Fil: Van Hegelsom, Rob. Ablynx nv; Bélgica
Fil: Stortelers, Catelijne. Ablynx nv; Bélgica
Fil: Bannas, Peter. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Koch Nolte, Friedrich. University Medical Center Hamburg-Eppendorf; Alemania
Materia
Nanobodies
CD38
Imaging
Neutralizing antibodies
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/53932
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/53932
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivoFumey, WilliamKoenigsdorf, JuliaKunick, ValentinMenzel, StephanSchütze, KerstinUnger, MandySchriewer, LevinHaag, FriedrichAdam, GerhardOberle, AnnaBinder, MaschaFliegert, RalfGuse, AndreasZhao, Yong JuanLee, Hon CheungMalavasi, FabioGoldbaum, Fernando AlbertoVan Hegelsom, RobStortelers, CatelijneBannas, PeterKoch Nolte, FriedrichNanobodiesCD38ImagingNeutralizing antibodieshttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3The 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.Fil: Fumey, William. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Koenigsdorf, Julia. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Kunick, Valentin. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Menzel, Stephan. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Schütze, Kerstin. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Unger, Mandy. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Schriewer, Levin. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Haag, Friedrich. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Adam, Gerhard. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Oberle, Anna. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Binder, Mascha. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Fliegert, Ralf. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Guse, Andreas. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Zhao, Yong Juan. Peking University; ChinaFil: Lee, Hon Cheung. Peking University; ChinaFil: Malavasi, Fabio. Università di Torino; ItaliaFil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; ArgentinaFil: Van Hegelsom, Rob. Ablynx nv; BélgicaFil: Stortelers, Catelijne. Ablynx nv; BélgicaFil: Bannas, Peter. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Koch Nolte, Friedrich. University Medical Center Hamburg-Eppendorf; AlemaniaNature Publishing Group2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53932Fumey, 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; 12-20172045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-14112-6info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-14112-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:17Zoai:ri.conicet.gov.ar:11336/53932instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:17.572CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo
title Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo
spellingShingle Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo
Fumey, William
Nanobodies
CD38
Imaging
Neutralizing antibodies
title_short Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo
title_full Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo
title_fullStr Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo
title_full_unstemmed Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo
title_sort Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo
dc.creator.none.fl_str_mv 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 Alberto
Van Hegelsom, Rob
Stortelers, Catelijne
Bannas, Peter
Koch Nolte, Friedrich
author Fumey, William
author_facet 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 Alberto
Van Hegelsom, Rob
Stortelers, Catelijne
Bannas, Peter
Koch Nolte, Friedrich
author_role author
author2 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 Alberto
Van Hegelsom, Rob
Stortelers, Catelijne
Bannas, Peter
Koch Nolte, Friedrich
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Nanobodies
CD38
Imaging
Neutralizing antibodies
topic Nanobodies
CD38
Imaging
Neutralizing antibodies
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Fumey, William. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Koenigsdorf, Julia. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Kunick, Valentin. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Menzel, Stephan. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Schütze, Kerstin. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Unger, Mandy. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Schriewer, Levin. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Haag, Friedrich. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Adam, Gerhard. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Oberle, Anna. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Binder, Mascha. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Fliegert, Ralf. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Guse, Andreas. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Zhao, Yong Juan. Peking University; China
Fil: Lee, Hon Cheung. Peking University; China
Fil: Malavasi, Fabio. Università di Torino; Italia
Fil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina
Fil: Van Hegelsom, Rob. Ablynx nv; Bélgica
Fil: Stortelers, Catelijne. Ablynx nv; Bélgica
Fil: Bannas, Peter. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Koch Nolte, Friedrich. University Medical Center Hamburg-Eppendorf; Alemania
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/53932
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
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/53932
identifier_str_mv 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
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-14112-6
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-14112-6
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269454005698560
score 13.13397

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