Laboratory of cell interactions
- Russia, Moscow, Ul. Miklukho-Maklaya 16/10 On the map
- IBCh RAS, build. 52, office. 457
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A method has been developed for the production of human NK cell clones using IL-2 and K562-mbIL21 feeder cells expressing membrane-bound IL-21
1. Using different models of clone cultivation, it was revealed that the cultivation conditions (the frequency of restimulation using feeder cells) affect the phenotype, functional characteristics, expansion level, and clone life expectancy, which can reach 14 weeks.
2. The CD57 marker can completely disappear from the cell surface of CD57-positive NK cells when cultured under stimulation conditions of IL-2 / K562-mbIL21.
3. Expression of the NKG2A receptor can occur de novo in the progeny of initially NKG2A-negative NK cells.
- (2019). Recurrent Stimulation of Natural Killer Cell Clones with K562 Expressing Membrane-Bound Interleukin-21 Affects Their Phenotype, Interferon-γ Production, and Lifespan. Int J Mol Sci 20 (2),
- (2018). Analysis of NK cell clones obtained using interleukin-2 and gene-modified K562 cells revealed the ability of. PLoS One 13 (12), e0208469
SUBPOPULATION OF HLA-DR-POSITIVE NK-CELLS CHARACTERIZED BY HIGH PROLIFERATIVE AND FUNCTIONAL ACTIVITY
In order to elaborate clones of cytotoxic lymphocytes for clinical application, a method has been developed for the expansion of NK cells using irradiated K562-mbIL21 cells expressing the membrane-bound form of IL-21. The distribution in the peripheral blood and the functional features of the HLA-DR+ NK cells, which are predominant in the populations of NK cells obtained using this method of stimulation, have been characterized.
- (2017). HLA-DR+NK cells are mostly characterized by less mature phenotype and high functional activity. Immunol Cell Biol 96 (2), 212–228
Retroviral gene transfer into primary human NK cells activated by IL-2 and K562 feeder cells expressing membrane-bound IL-21
Natural killer (NK) cells are capable of rapidly recognizing and efficiently killing tumor cells. This makes them a potentially promising agent for cancer immunotherapy. Additional genetic modifications of NK cells may further improve their anti-tumor efficacy. Numerous technical challenges associated with gene delivery into NK cells have significantly tempered this approach. We achieved efficient retroviral vector transduction of primary human NK cells that were stimulated by a combination of IL-2 and engineered K562 cells expressing membrane-bound IL-21. The activated NK cells were in less differentiated state and expressed NK cell activation receptors NKG2D, NKp30, CD16, and were highly HLA-DR-positive. This NK cell population was highly susceptible to the transduction by both GFP- and NGFR-expressing retroviral vectors. More mature CD57+ NK cell population was generally resistant to retroviral vector transduction because of poor response to the stimulation. Our findings may facilitate retroviral vector-mediated genetic engineering of human primary NK cells for future immunotherapies.
- (2017). Retroviral gene transfer into primary human NK cells activated by IL-2 and K562 feeder cells expressing membrane-bound IL-21. Immunotechnology 450, 90–94
Ethanol-dependent expression of the NKG2D ligands MICA/B in human cell lines and leukocytes
Stress-induced molecules MICA and MICB are capable to regulate activity of cytotoxic lymphocytes through the interaction with receptor NKG2D, which substantially affects the functionality of cellular immunity. In cell line models ethanol caused different changes in surface expression of MICA/B, particularly it induced the translocation of intracellular proteins MICA/B to the cell surface and shedding of MICA (in soluble and microparticle-associated forms) from the plasma membrane. The observed results are not linked with cell death in cultures, taking place only under higher doses of ethanol. Ethanol at physiologically relevant concentrations (and higher) stimulated expression of MICA/B genes in different cell types. Presumably, changes in MICA/B expression, caused by ethanol, can affect functions of NKG2D-positive cytotoxic lymphocytes, modulating immune reactions at excessive alcohol consumption.
- (2017). Ethanol-dependent expression of the NKG2D ligands MICA/B in human cell lines and leukocytes. Can J Biochem Cell Biol 95 (2), 280–288
- (2016). Циркулирующий белок MICА у больных злокачественными лимфомами. 18 (2), 151–162
The localization of positively and negatively charged chitosan nanoparticles in tumor cells has been characterized
In collaboration with Centre of Bioengineering RAS, Moscow
Using in vitro culture of RAW264 cells and nanoparticles fabricated from positive and negative chitosan derivations we demonstrated penetration of the particles into tumor cells and their intracellular localization: in mitochondria for positively charged nanoparticles and in lysosomes for negatively charged nanoparticles. Accumulation of both types of the particles resulted in reducing mitochondrial membrane potential and in exocytosis of mitochondria and lysosomes from live tumor cells. Our results suggest that positively charged chitosan derivates may be used for development of nanopreparations for treatment of the diseases with mitochondrial dysfunctions, and negatively charged chitosan derivates – for anticancer preparations.
Zubareva A.A., Shcherbinina T.S., Varlamov V.P., Svirshchevskaya E.V. Intracellular Sorting of Differently Charged Chitosan Derivatives and Chitosan-Based Nanoparticles. NanoScale. 2015 Nanoscale, 2015, 7, 7942 - 7952.