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

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1597
Author(s):  
Barbora Kalousková ◽  
Ondřej Skořepa ◽  
Denis Cmunt ◽  
Celeste Abreu ◽  
Kateřina Krejčová ◽  
...  

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.

2014 ◽  
Vol 5 ◽  
Author(s):  
Cristina Eguizabal ◽  
Olatz Zenarruzabeitia ◽  
Jorge Monge ◽  
Silvia Santos ◽  
Miguel Angel Vesga ◽  
...  

2015 ◽  
Vol 3 (S2) ◽  
Author(s):  
Xiaokui Zhang ◽  
Lin Kang ◽  
Ivana Djuretic ◽  
Eric Law ◽  
Vanessa Voskinarian-Berse ◽  
...  

2018 ◽  
Vol 14 (2) ◽  
pp. 100-104
Author(s):  
Bianca Dorana de Oliveira Souza ◽  
Brenda Francisconi Diaz ◽  
Gabriela Salvador Guidugli ◽  
Laura Socio Ferraz ◽  
Marla Karine Amarante ◽  
...  

2003 ◽  
Vol 197 (8) ◽  
pp. 967-976 ◽  
Author(s):  
Martin Prlic ◽  
Bruce R. Blazar ◽  
Michael A. Farrar ◽  
Stephen C. Jameson

While the specificity and development of natural killer (NK) cells have been intensely studied, little is known about homeostasis of the mature NK population. Here we show that mouse NK cells undergo homeostatic proliferation when transferred into NK-deficient Rag−/− γC−/− hosts. Normal NK functional activity is maintained during this process, although there are some changes in NK phenotype. Using cell sorting, we demonstrate that mature (Mac-1hi) NK cells undergo homeostatic proliferation in an NK-deficient environment, yet immature (Mac-1lo) NK cells also proliferate in such hosts. We find that mature NK cells survive but do not proliferate in hosts which possess an endogenous NK pool. However, we go on to show that mature NK survival is critically dependent on interleukin (IL)-15. Surprisingly, NK survival is also compromised after transfer of cells into IL-15Rα−/− mice, implying that IL-15 responsiveness by bystander cells is critical for NK maintenance. These data imply that, similar to T cells, homeostasis of the NK pool is much more dynamic than previously appreciated and this may be relevant to manipulation of NK cells for therapeutic purposes.


Lab on a Chip ◽  
2020 ◽  
Vol 20 (13) ◽  
pp. 2317-2327 ◽  
Author(s):  
Saheli Sarkar ◽  
Wenjing Kang ◽  
Songyao Jiang ◽  
Kunpeng Li ◽  
Somak Ray ◽  
...  

Comparative proteomic profiling and development of convolution neural network algorithm for quantifying discrete target interaction by engineered NK cells in microfluidic droplets.


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