A Novel Anti-Kv10.1 Nanobody Fused to Single-Chain TRAIL Enhances Apoptosis Induction in Cancer Cells
Antibody-based therapies hold promise for a safe and efficient treatment of cancer. The identification of target tumor cells through a specific antigen enriched on their surface and the subsequent delivery of the therapeutic agent only to those cells requires, besides the efficacy of the therapeutic...
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doaj-8a17bf723c6c4c479977eba27d8848872020-11-25T02:25:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-05-011110.3389/fphar.2020.00686542725A Novel Anti-Kv10.1 Nanobody Fused to Single-Chain TRAIL Enhances Apoptosis Induction in Cancer CellsFranziska Hartung0Thomas Krüwel1Xiaoyi Shi2Klaus Pfizenmaier3Roland Kontermann4Patrick Chames5Frauke Alves6Frauke Alves7Luis A. Pardo8Oncophysiology Group, Max Planck, Institute of Experimental Medicine, Göttingen, GermanyInstitute of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, GermanyOncophysiology Group, Max Planck, Institute of Experimental Medicine, Göttingen, GermanyInstitut für Zellbiologie und Immunologie, Universität Stuttgart, Stuttgart, GermanyInstitut für Zellbiologie und Immunologie, Universität Stuttgart, Stuttgart, GermanyAix Marseille Univ, CNRS, Inserm, Institut Paoli-Calmettes, CRCM, Marseille, FranceInstitute of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, GermanyTranslational Molecular Imaging Group, Max Planck Institute of Experimental Medicine, Göttingen, GermanyOncophysiology Group, Max Planck, Institute of Experimental Medicine, Göttingen, GermanyAntibody-based therapies hold promise for a safe and efficient treatment of cancer. The identification of target tumor cells through a specific antigen enriched on their surface and the subsequent delivery of the therapeutic agent only to those cells requires, besides the efficacy of the therapeutic agent itself, the identification of an antigen enriched on the surface of tumor cells, the generation of high affinity antibodies against that antigen. We have generated single-domain antibodies (nanobodies) against the voltage-gated potassium channel Kv10.1, which outside of the brain is detectable almost exclusively in tumor cells. The nanobody with highest affinity was fused to an improved form of the tumor necrosis factor-related apoptosis inducing ligand TRAIL, to target this cytokine to the surface of tumor cells. The resulting construct, VHH-D9-scTRAIL, shows rapid and strong apoptosis induction in different tumor models in cell culture. The construct combines two sources of specificity, the expression of the antigen restricted to tumor cells and the tumor selectivity of TRAIL. Such specificity combined with the high affinity obtained through nanobodies make the novel agent a promising concept for cancer therapy.https://www.frontiersin.org/article/10.3389/fphar.2020.00686/fulltargeted therapynanobodyTRAILKv10.1voltage-gated potassium channelapoptosis |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Franziska Hartung Thomas Krüwel Xiaoyi Shi Klaus Pfizenmaier Roland Kontermann Patrick Chames Frauke Alves Frauke Alves Luis A. Pardo |
spellingShingle |
Franziska Hartung Thomas Krüwel Xiaoyi Shi Klaus Pfizenmaier Roland Kontermann Patrick Chames Frauke Alves Frauke Alves Luis A. Pardo A Novel Anti-Kv10.1 Nanobody Fused to Single-Chain TRAIL Enhances Apoptosis Induction in Cancer Cells Frontiers in Pharmacology targeted therapy nanobody TRAIL Kv10.1 voltage-gated potassium channel apoptosis |
author_facet |
Franziska Hartung Thomas Krüwel Xiaoyi Shi Klaus Pfizenmaier Roland Kontermann Patrick Chames Frauke Alves Frauke Alves Luis A. Pardo |
author_sort |
Franziska Hartung |
title |
A Novel Anti-Kv10.1 Nanobody Fused to Single-Chain TRAIL Enhances Apoptosis Induction in Cancer Cells |
title_short |
A Novel Anti-Kv10.1 Nanobody Fused to Single-Chain TRAIL Enhances Apoptosis Induction in Cancer Cells |
title_full |
A Novel Anti-Kv10.1 Nanobody Fused to Single-Chain TRAIL Enhances Apoptosis Induction in Cancer Cells |
title_fullStr |
A Novel Anti-Kv10.1 Nanobody Fused to Single-Chain TRAIL Enhances Apoptosis Induction in Cancer Cells |
title_full_unstemmed |
A Novel Anti-Kv10.1 Nanobody Fused to Single-Chain TRAIL Enhances Apoptosis Induction in Cancer Cells |
title_sort |
novel anti-kv10.1 nanobody fused to single-chain trail enhances apoptosis induction in cancer cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2020-05-01 |
description |
Antibody-based therapies hold promise for a safe and efficient treatment of cancer. The identification of target tumor cells through a specific antigen enriched on their surface and the subsequent delivery of the therapeutic agent only to those cells requires, besides the efficacy of the therapeutic agent itself, the identification of an antigen enriched on the surface of tumor cells, the generation of high affinity antibodies against that antigen. We have generated single-domain antibodies (nanobodies) against the voltage-gated potassium channel Kv10.1, which outside of the brain is detectable almost exclusively in tumor cells. The nanobody with highest affinity was fused to an improved form of the tumor necrosis factor-related apoptosis inducing ligand TRAIL, to target this cytokine to the surface of tumor cells. The resulting construct, VHH-D9-scTRAIL, shows rapid and strong apoptosis induction in different tumor models in cell culture. The construct combines two sources of specificity, the expression of the antigen restricted to tumor cells and the tumor selectivity of TRAIL. Such specificity combined with the high affinity obtained through nanobodies make the novel agent a promising concept for cancer therapy. |
topic |
targeted therapy nanobody TRAIL Kv10.1 voltage-gated potassium channel apoptosis |
url |
https://www.frontiersin.org/article/10.3389/fphar.2020.00686/full |
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