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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
B. Kalousková, O. Skořepa, D. Cmunt, C. Abreu, K. Krejčová, J. Bláha, I. Sieglová, V. Král, M. Fábry, R. Pola, M. Pechar, O. Vaněk
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
18-10687S
Czech Science Foundation
LTC20078
The Ministry of Education, Youth and Sports of the Czech Republic
SVV 260427/2020
Charles University
GAUK 1740318
Charles University
PubMed Central od 2013
Europe PubMed Central od 2013
ProQuest Central od 2013-01-01
Open Access Digital Library od 2013-01-01
ROAD: Directory of Open Access Scholarly Resources od 2013
Odkazy
PubMed
34829829
DOI
10.3390/biomedicines9111597
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
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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- $a Kalousková, Barbora $u Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030, 12840 Prague, Czech Republic
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