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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8615638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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