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

Details

Serval ID
serval:BIB_F1D718EDAA50
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells.
Journal
Biomedicines
Author(s)
Kalousková B., Skořepa O., Cmunt D., Abreu C., Krejčová K., Bláha J., Sieglová I., Král V., Fábry M., Pola R., Pechar M., Vaněk O.
ISSN
2227-9059 (Print)
ISSN-L
2227-9059
Publication state
Published
Issued date
02/11/2021
Peer-reviewed
Oui
Volume
9
Number
11
Pages
1597
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Keywords
B7-H6, HPMA polymer, NK cell, NKp30, coiled coil, immunotherapy
Pubmed
Web of science
Open Access
Yes
Create date
10/12/2021 18:49
Last modification date
26/01/2022 7:36
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