Obtaining new feeder cell lines expressing membrane-bound forms of IL-12 and IL-18 to improve the anti-tumor properties of natural killer cells
Keywords:
natural killer cells, interleukins, feeder cell lines, acute leukemia, immunotherapyAbstract
Numerous clinical studies are currently underway on the use of natural killer cells in the treatment of cancer and solid tumors. However, such immunotherapy may be limited by the short persistence of natural killer cells in the host body and the ability of tumor cells to avoid recognition by natural killer cells. Solving these problems by modifying the initial properties of natural killer cells can significantly increase the effectiveness of antitumor therapy. One of the methods of modification is the use of new feeder cell lines expressing various combinations of membrane-bound cytokines (IL-12, IL-15, IL-18, IL-21) to obtain natural killer cells with a specific phenotype (memory-like). In the course of the work done, two new feeder cell lines based on K-562 cells with ectopic expression of a combination of interleukins IL-15, IL-12, IL-18 and IL-21, IL-12, IL-18 were obtained for the expansion of natural killer cells with enhanced antitumor activity.
References
- Abel AM, Yang C, Thakar MS, Malarkannan S. Natural killer cells: development, maturation, and clinical utilization. Frontiers in Immunology. 2018;9:1869. DOI: 10.3389/fimmu.2018.01869.
- Becker PSA, Suck G, Nowakowska P, Ullrich E, Seifried E, Bader P, et al. Selection and expansion of natural killer cells for NK cell-based immunotherapy. Cancer Immunology, Immunotherapy. 2016;65(4):477–484. DOI: 10.1007/s00262-016-1792-y.
- Vashkevich EP, Migas AA, Meleshko AN, Matveyenka MA, Strushkevich NV, Shman TV. Human natural killer cells expansion and activation ex vivo in the presence of transgenic feeder cell lines. Tsitologiya. 2020;62(4):258–265. Russian. DOI: 10.31857/S0041377120040070.
- Pahl JHW, Cerwenka A, Ni J. Memory-like NK cells: remembering a previous activation by cytokines and NK cell receptors. Frontiers in Immunology. 2018;9:2796. DOI: 10.3389/fimmu.2018.02796.
- Somanchi SS, Senyukov VV, Denman CJ, Lee DA. Expansion, purification, and functional assessment of human peripheral blood NK cells. Journal of Visualized Experiments. 2011;48:2540. DOI: 10.3791/2540.
- Shevtsova A. Evaluation of the effect of cytokines: IL-12, IL-18 and their combinations on the expansion, activation and functional activity of NK-cells. In: 14th Bialystok International Medical Congress for Young Scientists; 2019 May 17–18; Bialystok, Poland. Bialystok: [s. n.]; 2019. p. 79.
- Shevtsova AS. [Changing the properties of natural killer cells using genetically modified feeder cell lines for the purposes of antitumor immunotherapy]. In: Aktual’nye problemy i perspektivy razvitiya detskoi gematologii-onkologii v Rossiiskoi Federatsii. Sbornik materialov I Ob’edinennogo kongressa NODGO i RODO; 23–25 noyabrya 2020 g.; Moskva, Rossiya [Actual problems and prospects for the development of pediatric hematology and oncology in the Russian Federation. Collection of materials of the 1st Joint congress of NODGO and RODO; 2020 November 23–25; Moscow, Russia]. Moscow: National Society of Pediatric Hematologists and Oncologists; 2020. p. 110. Russian.
- Mukhametshina AS, Migas AA, Matveenko MA, Shman TV. [Creation and use of genetically engineered feeder cell lines for the expansion of natural killer cells with increased production of IFN-γ]. In: Goncharov AE, Skorobogatova AS, Poleshko AG, Martynova MA, Pinchuk SV, Bushmakina IM, et al., editors. Sovremennye problemy kletochnoi inzhenerii, immunologii i allergologii. Tezisy dokladov Mezhdunarodnoi nauchnoi konferentsii; 20–21 maya 2021 g.; Minsk, Belarus’ [Modern problems of cell engineering, immunology and allergology. Abstracts of the International scientific conference; 2021 May 20–21; Minsk, Belarus]. Minsk: [s. n.]; 2021. p. 36. Russian.
- Mukhametshyna N, Lasiukov Ya, Shman T. Harnessing genetically engineered feeder cell line for ex vivo expansion of human natural killer cells with increased production of IFN-γ. In: Juozaitytė E, editor. 7th Kaunas/Lithuania International Hematology/Oncology Colloquium; 2022 May 26; Kaunas, Lithuania. [S. l.]: [s. n.]; 2022. p. 10–11.
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