Medical Immunology (Russia), 2023, 25(5):1259-1264

UMBILICAL CORD BLOOD AS A PROMISING SOURCE OF NK CELLS FOR IMMUNOTHERAPY

Currently, a large number of studies on genetic modification of cord blood NK cells (UCB-NK) arecarried out at both clinical and preclinical levels. Immunotherapy based on UCB-NK cells has great potentialfor antitumor therapy. However, despite having known several advantages over peripheral blood NK cells (PB-NK), including a high concentration in cord blood and low virulence rate, UCB-NK cells are predominantlycharacterized in the scientific literature as immature and low-functioning NK cells. In this work, we studied thephenotypic characteristics of UCB-NK cells and the possibility of stimulatory compensation of the decreasedfunctional activity of UCB-NK cells. Our studies revealed UCB-NK cells can be characterized as poorlydifferentiated and weakly activated cells with high level of inhibitory receptor NKG2A and low level of activatingreceptor NKG2C and HLA-DR, accordingly with the literature data. Two types of stimuli were chosen tostimulate freshly isolated UCB-NK cells: 1) 100 units of IL-2; 2) combinations of 100 units IL-2 and K-562feeder cells expressing membrane-bound IL-21 (K562-mbIL21). It was shown the degranulation (LAMP-1)and proliferative activity was higher than for parallel cultured ex vivo PB-NK cells under the same conditionsfor UCB-NK cells stimulated for 7 days with IL-2 + K562-mbIL21. Moreover, stimulation in the way of IL-2 +K562-mbIL21 seemed to be a more perspective way to obtain a large number of proliferatively active UCB-NKcells compared to stimulation with IL-2 only. Since genetic modification of NK cells is a promising way toimprove the antitumor properties of NK cells, retroviral transduction procedure was performed to study of thestimulated UCB-NK cells. UCB-NK cells stimulated with IL-2 + K562-mbIL21 were transduced on day 8 ofcultivation. In this study, we used targeted overexpression of the adaptor molecule DAP12, which is involved in the signaling of activating NK cell receptors. PB-NK cells and UCB-NK cells were transduced under the equalexperimental conditions in same volume of viral particles. As a result, the transduction efficiency was found tobe more than 4-fold higher for UCB-NK cells compared to PB-NK cells. Thus, UCB-NK cells appear to be apromising tool for further research in cancer immunotherapy.

IBCH: 10830
Ссылка на статью в журнале: https://www.mimmun.ru/mimmun/article/view/2846
Кол-во цитирований на 10.2024: 0
Данные статьи проверены модераторами 2023-08-28

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