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

0552098 - ÚMG 2022 RIV CH eng J - Journal Article
Kalousková, B. - Skořepa, O. - Cmunt, D. - Abreu, C. - Krejčová, K. - Blaha, J. - Sieglová, Irena - Král, Vlastimil - Fábry, Milan - Pola, Robert - Pechar, Michal - Vaněk, O.
Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells.
Biomedicines. Roč. 9, č. 11 (2021), č. článku 1597. E-ISSN 2227-9059
R&D Projects: GA ČR(CZ) GA18-10687S; GA ČR(CZ) GA21-11688S; GA MŠMT(CZ) LM2018127
Research Infrastructure: CIISB II - 90127
Institutional support: RVO:68378050 ; RVO:61389013
Keywords : coiled coil * HPMA polymer * NK cell * NKp30 * b7-h6 * immunotherapy
OECD category: Biochemistry and molecular biology; Polymer science (UMCH-V)
Impact factor: 4.757, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2227-9059/9/11/1597

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.
Permanent Link: http://hdl.handle.net/11104/0327244