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

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 hema...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-10, Vol.7 (1), p.14289-13, Article 14289
Main Authors: 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, Cheung Lee, Hon, Malavasi, Fabio, Goldbaum, Fernando, van Hegelsom, Rob, Stortelers, Catelijne, Bannas, Peter, Koch-Nolte, Friedrich
Format: Article
Language:English
Subjects:
ADP-ribosyl Cyclase 1 - immunology
ADP-ribosyl Cyclase 1 - metabolism
Animal models
Animals
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents - therapeutic use
Camelids, New World
CD38 antigen
Cell culture
Cell Line, Tumor
Cell surface
Cell Surface Display Techniques
Disease Models, Animal
Enzymatic activity
Epitopes
Epitopes - immunology
Fluorescent Dyes
Hematology
Humans
Intravenous administration
Membrane Glycoproteins - immunology
Membrane Glycoproteins - metabolism
Mice
Mice, Nude
Multiple myeloma
Multiple Myeloma - diagnosis
Multiple Myeloma - drug therapy
Multiple Myeloma - pathology
Nanobodies
Phage display
Rodents
Single-Domain Antibodies - immunology
Tumors
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-14112-6