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VAV1‐overexpressing YT cells display improved cytotoxicity against malignant cells
Author(s) -
Smagina Anna S.,
Kulemzin Sergey V.,
Yusubalieva Gaukhar M.,
Kedrova Anna G.,
Sanzharov Andrey E.,
Ivanov Yurii V.,
Matvienko Darya A.,
Kalsin Vladimir A.,
Gorchakov Andrey A.,
Baklaushev Vladimir P.,
Taranin Aleksandr V.
Publication year - 2021
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1002/bab.2001
Subject(s) - cytotoxicity , chimeric antigen receptor , cancer research , homing (biology) , genetically engineered , cell culture , immunotherapy , cancer cell , cytotoxic t cell , adoptive cell transfer , cell therapy , in vitro , immunology , cell , chemistry , biology , medicine , cancer , immune system , biochemistry , ecology , genetics , gene
Immunotherapy based on adoptive transfer of genetically engineered T‐ and NK‐cells is an area of active ongoing research and has proven highly efficacious for patients with certain B‐cell malignancies. Use of NK cells and NK cell lines as carriers of chimeric antigen receptors (CARs) appears particularly promising, as this opens an opportunity for moving the therapy from autologous to the allogeneic (universal) format. This “off‐the‐shelf” approach is thought to significantly reduce the price of the treatment and make it available to many more patients in need. Yet, the efficacy of CAR‐NK cells in vivo presently remains low, and boosting the activity of CAR NK cells via stronger tumor homing, resistance to tumor microenvironment, as well as greater cytotoxicity may translate into improved patient outcomes. Here, we established a derivative of a human NK cell line YT overexpressing a positive regulator of cytotoxicity, VAV1. Activity of YT‐VAV1 cells obtained was assayed in vitro against several cancer cell lines and primary patient‐derived cancer cells. YT‐VAV1 cells outperform parental YT cells in terms of cytotoxicity.