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:	Barbora Kalousková, Ondřej Skořepa, Denis Cmunt, Celeste Abreu, Kateřina Krejčová, Jan Bláha, Irena Sieglová, Vlastimil Král, Milan Fábry, Robert Pola, Michal Pechar, Ondřej Vaněk
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	coiled coil HPMA polymer NK cell NKp30 B7-H6 immunotherapy Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2c9043d3a1e7484f806ef4bdcff6e30e
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spelling	oai:doaj.org-article:2c9043d3a1e7484f806ef4bdcff6e30e2021-11-25T16:49:29ZTumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells10.3390/biomedicines91115972227-9059https://doaj.org/article/2c9043d3a1e7484f806ef4bdcff6e30e2021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1597https://doaj.org/toc/2227-9059Targeted 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 <i>in vitro</i> 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.Barbora KalouskováOndřej SkořepaDenis CmuntCeleste AbreuKateřina KrejčováJan BláhaIrena SieglováVlastimil KrálMilan FábryRobert PolaMichal PecharOndřej VaněkMDPI AGarticlecoiled coilHPMA polymerNK cellNKp30B7-H6immunotherapyBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1597, p 1597 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	coiled coil HPMA polymer NK cell NKp30 B7-H6 immunotherapy Biology (General) QH301-705.5
spellingShingle	coiled coil HPMA polymer NK cell NKp30 B7-H6 immunotherapy Biology (General) QH301-705.5 Barbora Kalousková Ondřej Skořepa Denis Cmunt Celeste Abreu Kateřina Krejčová Jan Bláha Irena Sieglová Vlastimil Král Milan Fábry Robert Pola Michal Pechar Ondřej Vaněk Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells
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 <i>in vitro</i> 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	article
author	Barbora Kalousková Ondřej Skořepa Denis Cmunt Celeste Abreu Kateřina Krejčová Jan Bláha Irena Sieglová Vlastimil Král Milan Fábry Robert Pola Michal Pechar Ondřej Vaněk
author_facet	Barbora Kalousková Ondřej Skořepa Denis Cmunt Celeste Abreu Kateřina Krejčová Jan Bláha Irena Sieglová Vlastimil Král Milan Fábry Robert Pola Michal Pechar Ondřej Vaněk
author_sort	Barbora Kalousková
title	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_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_sort	tumor marker b7-h6 bound to the coiled coil peptide-polymer conjugate enables targeted therapy by activating human natural killer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2c9043d3a1e7484f806ef4bdcff6e30e
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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

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