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

Scientific Reports
William FumeyFriedrich Koch-Nolte

Abstract

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.

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Citations

Apr 11, 2018·The Journal of Biological Chemistry·Cheng FangYong Juan Zhao
Nov 21, 2018·The Biochemical Journal·Martin A RossottiC Roger MacKenzie
Jul 8, 2020·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Vanessa F Arnaud-SampaioClaudiana Lameu
Feb 8, 2018·Frontiers in Immunology·Thomas EdenFriedrich Koch-Nolte
Apr 11, 2018·Frontiers in Pharmacology·Stephan MenzelFriedrich Koch-Nolte
Nov 22, 2018·Frontiers in Immunology·Peter Bannas, Friedrich Koch-Nolte
Dec 14, 2018·Frontiers in Immunology·Fabio MorandiFabio Malavasi
Jan 4, 2021·Biochemical Pharmacology·Marie EggersFriedrich Koch-Nolte
Feb 6, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Cheng WangWeijun Wei
Feb 12, 2021·Biomolecules·Chaolemeng BaoXian-Hui Wu
Dec 18, 2020·Frontiers in Immunology·Zayda L Piedra-QuinteroMireia Guerau-de-Arellano
Apr 2, 2021·International Journal of Nanomedicine·Shuyang SunXiaoling Lu
May 13, 2021·Immunity, Inflammation and Disease·Julia HambachFriedrich Koch-Nolte
Jun 17, 2021·Cell and Tissue Research·Nicola WannerFriedrich Koch-Nolte
Jun 20, 2021·Molecular Diagnosis & Therapy·Nairo Brilhante-da-SilvaSoraya Dos Santos Pereira
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Sep 11, 2021·Frontiers in Immunology·África Martínez-BlancoJaime Sancho
Dec 5, 2020·Seminars in Immunology·Elisha R VerhaarHidde L Ploegh

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Methods Mentioned

BETA
phage display
transfection
bio-layer interferometry
flow cytometry
Biosensors
xenograft
glycosylation
ELISA
fluorescence activated cell sorting
PCR

Software Mentioned

PyMOL
Living Image
Spotfire
Treestar
Dara
Octet
ForteBio Data Analysis
FlowJo

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