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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Bibliographic Details
Published in:Biomedicines 2021-11, Vol.9 (11), p.1597
Main Authors: Kalousková, Barbora, Skořepa, Ondřej, Cmunt, Denis, Abreu, Celeste, Krejčová, Kateřina, Bláha, Jan, Sieglová, Irena, Král, Vlastimil, Fábry, Milan, Pola, Robert, Pechar, Michal, Vaněk, Ondřej
Format: Article
Language:English
Subjects:
Apoptosis
B7-H6
Biological activity
Biomarkers
Biopolymers
Breast cancer
Calorimetry
Cancer
Cancer immunotherapy
Cancer therapies
coiled coil
Copolymers
Cytotoxicity
FasL protein
HPMA polymer
Immune system
Immunosurveillance
Immunotherapy
Ligands
Lymphocytes
Lymphoma
Monoclonal antibodies
Natural killer cells
NK cell
NKp30
Peptides
Polymers
Proteins
Stoichiometry
T cell receptors
Titration
Tumor cell lines
Tumor cells
Tumor markers
Tumors
Ultracentrifugation
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Summary: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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9111597