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Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33

Nanobodies (Nbs) are the smallest antigen-binding, single domain fragments derived from heavy-chain-only antibodies from Camelidae. Among the several advantages over conventional monoclonal antibodies, their small size (12–15 kDa) allows them to extravasate rapidly, to show improved tissue penetrati...

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Autores principales: Romão, Ema, Krasniqi, Ahmet, Maes, Laila, Vandenbrande, Camille, Sterckx, Yann G.-J., Stijlemans, Benoit, Vincke, Cécile, Devoogdt, Nick, Muyldermans, Serge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981622/
https://www.ncbi.nlm.nih.gov/pubmed/31906437
http://dx.doi.org/10.3390/ijms21010310
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author Romão, Ema
Krasniqi, Ahmet
Maes, Laila
Vandenbrande, Camille
Sterckx, Yann G.-J.
Stijlemans, Benoit
Vincke, Cécile
Devoogdt, Nick
Muyldermans, Serge
author_facet Romão, Ema
Krasniqi, Ahmet
Maes, Laila
Vandenbrande, Camille
Sterckx, Yann G.-J.
Stijlemans, Benoit
Vincke, Cécile
Devoogdt, Nick
Muyldermans, Serge
author_sort Romão, Ema
collection PubMed
description Nanobodies (Nbs) are the smallest antigen-binding, single domain fragments derived from heavy-chain-only antibodies from Camelidae. Among the several advantages over conventional monoclonal antibodies, their small size (12–15 kDa) allows them to extravasate rapidly, to show improved tissue penetration, and to clear rapidly from blood, which are important characteristics for cancer imaging and targeted radiotherapy. Herein, we identified Nbs against CD33, a marker for acute myeloid leukemia (AML). A total of 12 Nbs were generated against recombinant CD33 protein, out of which six bound natively CD33 protein, expressed on the surface of acute myeloid leukemia THP-1 cells. The equilibrium dissociation constants (K(D)) of these six Nbs and CD33 range from 4 to 270 nM, and their melting temperature (Tm) varies between 52.67 and 67.80 °C. None of these Nbs showed leukemogenicity activity in vitro. The selected six candidates were radiolabeled with (99m)Tc, and their biodistribution was evaluated in THP-1-tumor-bearing mice. The imaging results demonstrated the fast tumor-targeting capacity of the Nbs in vivo. Among the anti-CD33 Nbs, Nb_7 showed the highest tumor uptake (2.53 ± 0.69 % injected activity per gram (IA/g), with low background signal, except in the kidneys and bladder. Overall, Nb_7 exhibits the best characteristics to be used as an anti-CD33 targeting vehicle for future diagnostic or therapeutic applications.
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spelling pubmed-69816222020-02-03 Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33 Romão, Ema Krasniqi, Ahmet Maes, Laila Vandenbrande, Camille Sterckx, Yann G.-J. Stijlemans, Benoit Vincke, Cécile Devoogdt, Nick Muyldermans, Serge Int J Mol Sci Article Nanobodies (Nbs) are the smallest antigen-binding, single domain fragments derived from heavy-chain-only antibodies from Camelidae. Among the several advantages over conventional monoclonal antibodies, their small size (12–15 kDa) allows them to extravasate rapidly, to show improved tissue penetration, and to clear rapidly from blood, which are important characteristics for cancer imaging and targeted radiotherapy. Herein, we identified Nbs against CD33, a marker for acute myeloid leukemia (AML). A total of 12 Nbs were generated against recombinant CD33 protein, out of which six bound natively CD33 protein, expressed on the surface of acute myeloid leukemia THP-1 cells. The equilibrium dissociation constants (K(D)) of these six Nbs and CD33 range from 4 to 270 nM, and their melting temperature (Tm) varies between 52.67 and 67.80 °C. None of these Nbs showed leukemogenicity activity in vitro. The selected six candidates were radiolabeled with (99m)Tc, and their biodistribution was evaluated in THP-1-tumor-bearing mice. The imaging results demonstrated the fast tumor-targeting capacity of the Nbs in vivo. Among the anti-CD33 Nbs, Nb_7 showed the highest tumor uptake (2.53 ± 0.69 % injected activity per gram (IA/g), with low background signal, except in the kidneys and bladder. Overall, Nb_7 exhibits the best characteristics to be used as an anti-CD33 targeting vehicle for future diagnostic or therapeutic applications. MDPI 2020-01-02 /pmc/articles/PMC6981622/ /pubmed/31906437 http://dx.doi.org/10.3390/ijms21010310 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Romão, Ema
Krasniqi, Ahmet
Maes, Laila
Vandenbrande, Camille
Sterckx, Yann G.-J.
Stijlemans, Benoit
Vincke, Cécile
Devoogdt, Nick
Muyldermans, Serge
Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33
title Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33
title_full Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33
title_fullStr Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33
title_full_unstemmed Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33
title_short Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33
title_sort identification of nanobodies against the acute myeloid leukemia marker cd33
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981622/
https://www.ncbi.nlm.nih.gov/pubmed/31906437
http://dx.doi.org/10.3390/ijms21010310
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