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Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells

Targeted cancer immunotherapy is a promising tool for restoring immune surveillance and eradicating cancer cells. Hydrophilic polymers modified with coiled coil peptide tags can be used as universal carriers designed for cell-specific delivery of such biologically active proteins. Here, we describe...

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Autores principales: Kalousková, Barbora, Skořepa, Ondřej, Cmunt, Denis, Abreu, Celeste, Krejčová, Kateřina, Bláha, Jan, Sieglová, Irena, Král, Vlastimil, Fábry, Milan, Pola, Robert, Pechar, Michal, Vaněk, Ondřej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615638/
https://www.ncbi.nlm.nih.gov/pubmed/34829829
http://dx.doi.org/10.3390/biomedicines9111597
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author Kalousková, Barbora
Skořepa, Ondřej
Cmunt, Denis
Abreu, Celeste
Krejčová, Kateřina
Bláha, Jan
Sieglová, Irena
Král, Vlastimil
Fábry, Milan
Pola, Robert
Pechar, Michal
Vaněk, Ondřej
author_facet Kalousková, Barbora
Skořepa, Ondřej
Cmunt, Denis
Abreu, Celeste
Krejčová, Kateřina
Bláha, Jan
Sieglová, Irena
Král, Vlastimil
Fábry, Milan
Pola, Robert
Pechar, Michal
Vaněk, Ondřej
author_sort Kalousková, Barbora
collection PubMed
description Targeted cancer immunotherapy is a promising tool for restoring immune surveillance and eradicating cancer cells. Hydrophilic polymers modified with coiled coil peptide tags can be used as universal carriers designed for cell-specific delivery of such biologically active proteins. Here, we describe the preparation of pHPMA-based copolymer conjugated with immunologically active protein B7-H6 via complementary coiled coil VAALEKE (peptide E) and VAALKEK (peptide K) sequences. Receptor B7-H6 was described as a binding partner of NKp30, and its expression has been proven for various tumor cell lines. The binding of B7-H6 to NKp30 activates NK cells and results in Fas ligand or granzyme-mediated apoptosis of target tumor cells. In this work, we optimized the expression of coiled coil tagged B7-H6, its ability to bind activating receptor NKp30 has been confirmed by isothermal titration calorimetry, and the binding stoichiometry of prepared chimeric biopolymer has been characterized by analytical ultracentrifugation. Furthermore, this coiled coil B7-H6-loaded polymer conjugate activates NK cells in vitro and, in combination with coiled coil scFv, enables their targeting towards a model tumor cell line. Prepared chimeric biopolymer represents a promising precursor for targeted cancer immunotherapy by activating the cytotoxic activity of natural killer cells.
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spelling pubmed-86156382021-11-26 Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells Kalousková, Barbora Skořepa, Ondřej Cmunt, Denis Abreu, Celeste Krejčová, Kateřina Bláha, Jan Sieglová, Irena Král, Vlastimil Fábry, Milan Pola, Robert Pechar, Michal Vaněk, Ondřej Biomedicines Article Targeted cancer immunotherapy is a promising tool for restoring immune surveillance and eradicating cancer cells. Hydrophilic polymers modified with coiled coil peptide tags can be used as universal carriers designed for cell-specific delivery of such biologically active proteins. Here, we describe the preparation of pHPMA-based copolymer conjugated with immunologically active protein B7-H6 via complementary coiled coil VAALEKE (peptide E) and VAALKEK (peptide K) sequences. Receptor B7-H6 was described as a binding partner of NKp30, and its expression has been proven for various tumor cell lines. The binding of B7-H6 to NKp30 activates NK cells and results in Fas ligand or granzyme-mediated apoptosis of target tumor cells. In this work, we optimized the expression of coiled coil tagged B7-H6, its ability to bind activating receptor NKp30 has been confirmed by isothermal titration calorimetry, and the binding stoichiometry of prepared chimeric biopolymer has been characterized by analytical ultracentrifugation. Furthermore, this coiled coil B7-H6-loaded polymer conjugate activates NK cells in vitro and, in combination with coiled coil scFv, enables their targeting towards a model tumor cell line. Prepared chimeric biopolymer represents a promising precursor for targeted cancer immunotherapy by activating the cytotoxic activity of natural killer cells. MDPI 2021-11-02 /pmc/articles/PMC8615638/ /pubmed/34829829 http://dx.doi.org/10.3390/biomedicines9111597 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kalousková, Barbora
Skořepa, Ondřej
Cmunt, Denis
Abreu, Celeste
Krejčová, Kateřina
Bláha, Jan
Sieglová, Irena
Král, Vlastimil
Fábry, Milan
Pola, Robert
Pechar, Michal
Vaněk, Ondřej
Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells
title Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells
title_full Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells
title_fullStr Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells
title_full_unstemmed Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells
title_short Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells
title_sort tumor marker b7-h6 bound to the coiled coil peptide-polymer conjugate enables targeted therapy by activating human natural killer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615638/
https://www.ncbi.nlm.nih.gov/pubmed/34829829
http://dx.doi.org/10.3390/biomedicines9111597
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