CAR НК-терапия: методы активации и экспансии НК-клеток
https://doi.org/10.29413/ABS.2024-9.5.6
Аннотация
На сегодняшний день терапия Т-клетками с химерным рецептором антигена (CAR, chimeric antigen receptor) представляет собой эффективный метод лечения в области онкогематологических заболеваний. Однако иммунотерапия на основе Т-лимфоцитов имеет определённые недостатки, ограничивающие область применения данного подхода. Многообещающей альтернативой служит основанная на натуральных киллерах (НК-клетках) CAR-терапия, поскольку она не требует детального подбора донора по системе человеческих лейкоцитарных антигенов; НК-клетки обладают уникальным механизмом распознавания и уничтожения опухолевых клеток. Кроме того, при инфузии натуральные киллеры не вызывают тяжёлых токсических реакций. Создание CAR НК-продукта представляет собой непростую задачу, включающую культивирование клеток, использование методов генной инженерии, а также проверку контроля качества полученного биомедицинского клеточного продукта (БМКП). Для пролиферации и усиления эффекторных функций НК-клеткам требуется наличие в питательной среде интерлейкинов, фидерных клеток или их компонентов и активаторов иммунной системы. В данном обзоре основное внимание уделяется различным подходам к активации и экспансии натуральных киллеров в процессе культивирования, а также затрагиваются вопросы о достоинствах и недостатках выбранного метода терапии и о регуляторных аспектах создания полноценного БМКП.
Ключевые слова
адоптивная иммунотерапия,
химерные антигенные рецепторы,
НК-клетки,
фидерные клетки,
интерлейкины,
трансдукция
При поддержке: Автор выражает благодарность коллективу лаборатории клеточного иммунитета Научно-исследовательского института экспериментальной диагностики и терапии опухолей ФГБУ «Научный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России за помощь в написании данной работы.
Об авторе
П. О. Фёдорова
ФГБНУ «Научно-исследовательский институт вакцин и сывороток им. И.И. Мечникова»; Научно-исследовательский институт экспериментальной диагностики и терапии опухолей, ФГБУ «Научный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России; ФГАОУ ВО Первый Московский
государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)
Россия
Россия
Фёдорова Полина Олеговна – младший научный сотрудник лаборатории прикладной вирусологии, аспирант; лаборант-исследователь лаборатории клеточного иммунитета; ассистент кафедры микробиологии, вирусологии и иммуннологии
105064, г. Москва, Малый Казенный пер., 5А
115522, г. Москва, Каширское шоссе, д. 24
119991, г. Москва, ул. Трубецкая, 8, стр. 2
Список литературы
1. Cianga VA, Campos Catafal L, Cianga P, Pavel Tanasa M, Cherry M, Collet P, et al. Natural killer cell subpopulations and inhibitory receptor dynamics in myelodysplastic syndromes and acute myeloid leukemia. Front Immunol. 2021; 12: 665541. doi: 10.3389/fimmu.2021.665541
2. Грибкова И.В. CAR NK-клетки и возможность их использования для лечения гематологических новообразований. Современная онкология. 2022; 24(3): 331-335.
3. Jorgovanovic D, Song M, Wang L, Zhang Y. Roles of IFN-γ in tumor progression and regression: A review. Biomark Res. 2020; 8: 49. doi: 10.1186/s40364-020-00228-x
4. D’Silva SZ, Singh M, Pinto AS. NK cell defects: Implication in acute myeloid leukemia. Front Immunol. 2023; 14: 1112059. doi: 10.3389/fimmu.2023.1112059
5. Zhang L, Meng Y, Feng X, Han Z. CAR-NK cells for cancer immunotherapy: From bench to bedside. Biomark Res. 2022; 10(1): 12. doi: 10.1186/s40364-022-00364-6
6. Torelli GF, Rozera C, Santodonato L, Peragine N, D’Agostino G, Montefiore E, et al. A good manufacturing practice method to ex vivo expand natural killer cells for clinical use. Blood Transfus. 2015; 13: 464-471. doi: 10.2450/ 2015.0231-14
7. Yang YL, Yang F, Huang ZQ, Li YY, Shi HY, Sun Q, et al. T cells, NK cells, and tumor-associated macrophages in cancer immunotherapy and the current state of the art of drug delivery systems. Front Immunol. 2023; 14: 1199173. doi: 10.3389/fimmu.2023.1199173
8. Khawar MB, Sun H. CAR-NK cells: From natural basis to design for kill. Front Immunol. 2021; 12: 707542. doi: 10.3389/fimmu.2021.707542
9. Chohan KL, Siegler EL, Kenderian SS. CAR-T cell therapy: The efficacy and toxicity balance. Curr Hematol Malig Rep. 2023; 18(2): 9-18. doi: 10.1007/s11899-023-00687-7
10. Yu Y. The function of NK cells in tumor metastasis and NK cell-based immunotherapy. Cancers (Basel). 2023; 15(8): 2323. doi: 10.3390/cancers15082323
11. Carlsten M, Childs RW. Genetic manipulation of NK cells for cancer immunotherapy: Techniques and clinical implications. Front Immunol. 2015; 6: 266. doi: 10.3389/fimmu.2015.00266
12. Киселевский М.В., Чикилева И.О., Ситдикова С.М., Власенко Р.Я., Караулов А.В. Перспективы применения генетически модифицированных лимфоцитов с химерным Т-клеточным рецептором (CAR-T-клеток) для терапии солидных опухолей. Иммунология. 2019; 40(4): 48-55.
13. Duan D, Wang K, Wei C, Feng D, Liu Y, He Q, et al. The BCMAtargeted fourth-generation CAR-T cells secreting IL-7 and CCL19 for therapy of refractory/recurrent multiple myeloma. Front Immunol. 2021; 12: 609421. doi: 10.3389/fimmu.2021.609421
14. Кочнева Г.В., Сиволобова Г.Ф., Ткачева А.В., Горчаков А.А., Кулемзин С.В. Комбинированная терапия рака на основе онколитической виротерапии и таргетной CAR T/NK-клеточной иммунотерапии. Молекулярная биология. 2020; 54(1): 3-16.
15. Fitzgerald JC, Weiss SL, Maude SL, Barrett DM, Lacey SF, Melenhorst JJ, et al. Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit Care Med. 2017; 45(2): e124-e131. doi: 10.1097/CCM.0000000000002053
16. Nazimuddin F, Finklestein JM, Gupta M, Kulikovskaya I, Ambrose DE, Gill S, et al. Long-term functional persistence, B cell aplasia and anti-leukemia efficacy in refractory B cell malignancies following T cell immunotherapy using CAR-redirected T cells targeting CD19. Blood. 2013; 122 (21): 163. doi: 10.1182/blood.V122.21.163.163
17. Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med. 2020; 382(6): 545-553. doi: 10.1056/NEJMoa1910607
18. Marin D, Li Y, Basar R, Rafei H, Daher M, Dou J, et al. Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: A phase 1/2 trial. Nat Med. 2024; 30(3): 772-784. doi: 10.1038/s41591-023-02785-8
19. Pedroza-Pacheco I, Madrigal A, Saudemont A. Interaction between natural killer cells and regulatory T cells: Perspectives for immunotherapy. Cell Mol Immunol. 2013; 10(3): 222-229. doi: 10.1038/cmi.2013.2
20. Matosevic S. Viral and nonviral engineering of natural killer cells as emerging adoptive cancer immunotherapies. J Immunol Res. 2018; 2018: 678-689. doi: 10.1155/2018/4054815
21. Liu E, Tong Y, Dotti G, Shaim H, Savoldo B, Mukherjee M, et al. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia. 2018; 32(2): 520-531. doi: 10.1038/leu.2017.226
22. Romee R, Schneider SE, Leong JW, Chase JM, Keppel CR, Sullivan RP, et al. Cytokine activation induces human memorylike NK cells. Blood. 2012; 120(24): 4751-4760. doi: 10.1182/blood-2012-04-419283
23. Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA, Schappe T, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Trans Med. 2016; 8(357): 357ra123-357ra123. doi: 10.1126/scitranslmed.aaf2341
24. Castriconi R, Carrega P, Dondero A, Bellora F, Casu B, Regis S, et al. Molecular mechanisms directing migration and retention of natural killer cells in human tissues. Front Immunol. 2018; 9: 2324. doi: 10.3389/fimmu.2018.02324
25. Marofi F, Abdul-Rasheed OF, Rahman HS, Budi HS, Jalil AT, Yumashev AV, et al. CAR-NK cell in cancer immunotherapy: A promising frontier. Cancer Sci. 2021; 112(9): 3427-3436. doi: 10.1111/cas.14993
26. Daher M, Basar R, Shaim H, Gokdemir E, Uprety N, Kontoyiannis A, et al. The TGF-b/SMAD signaling pathway as a mediator of NK cell dysfunction and immune evasion in myelodysplastic syndrome. Blood. 2017; 130(Suppl 1): 53. doi: 10.1182/blood.V130.Suppl_1.53.53.
27. Young A, Ngiow SF, Gao Y, Patch A-M, Barkauskas DS, Messaoudene M, et al. A2AR adenosine signaling suppresses natural killer cell maturation in the tumor microenvironment. Cancer Res. 2018; 78(4): 1003-1016. doi: 10.1158/0008-5472.CAN-17-2826
28. Xie G, Dong H, Liang Y, Ham JD, Rizwan R, Chen J. CAR-NK cells: A promising cellular immunotherapy for cancer. EBioMedicine. 2020; 59: 102975. doi: 10.1016/j.ebiom.2020.102975
29. Nanbakhsh A, Best B, Riese M, Rao S, Wang L, Medin J, et al. Dextran enhances the lentiviral transduction efficiency of murine and human primary NK cells. J Vis Exp. 2018; (131): 55063. doi: 10.3791/55063
30. Laskowski TJ, Biederstädt A, Rezvani K. Natural killer cells in antitumour adoptive cell immunotherapy. Nat Rev Cancer. 2022; 22(10): 557-575. doi: 10.1038/s41568-022-00491-0
31. Merino A, Maakaron J, Bachanova V. Advances in NK cell therapy for hematologic malignancies: NK source, persistence and tumor targeting. Blood Rev. 2023; 60: 101073. doi: 10.1016/j.blre.2023.101073
32. Chabannon C, Mfarrej B, Guia S, Ugolini S, Devillier R, Blaise D, et al. Manufacturing natural killer cells as medicinal products. Front Immunol. 2016; 7: 504. doi: 10.3389/fimmu.2016.00504
33. Berrien-Elliott MM, Jacobs MT, Fehniger TA. Allogeneic natural killer cell therapy. Blood. 2023; 141(8): 856-868. doi: 10.1182/blood.2022016200
34. Vasu S, Berg M, Davidson-Moncada J, Tian X, Cullis H, Childs RW. A novel method to expand large numbers of CD56(+) natural killer cells from a minute fraction of selectively accessed cryopreserved cord blood for immunotherapy after transplantation. Cytotherapy. 2015; 17(11): 1582-1593. doi: 10.1016/j.jcyt.2015.07.020
35. Eguizabal C, Zenarruzabeitia O, Monge J, Santos S, Vesga MA, Maruri N, et al. Natural killer cells for cancer immunotherapy: pluripotent stem cells-derived NK cells as an immunotherapeutic perspective. Front Immunol. 2014; 5: 439. doi: 10.3389/fimmu.2014.00439
36. Kotzur R, Duev-Cohen A, Kol I, Reches A, Mandelboim O, Stein N. NK-92 cells retain vitality and functionality when grown in standard cell culture conditions. PLoS One. 2022; 17(3): e0264897. doi: 10.1371/journal.pone.0264897
37. Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013; 15(12): 1563-1570. doi: 10.1016/j.jcyt.2013.06.017
38. Zhang Y, Zhou W, Yang J, Yang J, Wang W. Chimeric antigen receptor engineered natural killer cells for cancer therapy. Exp Hematol Oncol. 2023; 12(1): 70. doi: 10.1186/s40164-023-00431-0
39. Rölle A, Pollmann J, Ewen E, Le VTK, Halenius A, Hengel H, et al. IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion. J Clin Invest. 2014; 124: 5305-5316. doi: 10.1172/JCI77440
40. Huenecke S, Zimmermann SY, Kloess S, Esser R, Brinkmann A, Tramsen L, et al. IL-2-driven regulation of NK cell receptors with regard to the distribution of CD16+ and CD16– subpopulations and in vivo influence after haploidentical NK cell infusion. J Immunother. 2010; 33: 200-210. doi: 10.1097/ CJI.0b013e3181bb46f7
41. Koehl U, Brehm C, Huenecke S, Zimmermann S-Y, Kloess S, Bremm M, et al. Clinical grade purification and expansion of NK cell products for an optimized manufacturing protocol. Front Oncol. 2013; 3: 118. doi: 10.3389/fonc.2013.00118
42. Koehl U, Kalberer C, Spanholtz J, Lee D, Miller J, Cooley S, et al. Advances in clinical NK cell studies: Donor selection, manufacturing and quality control. Oncoimmunology. 2015; 5(4): e1115178. doi: 10.1080/2162402X.2015.1115178
43. Conlon KC, Lugli E, Welles HC, Rosenberg SA, Fojo AT, Morris JC, et al. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-inhuman clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol. 2015; 33(1): 74-82. doi: 10.1200/JCO.2014.57.3329
44. Mao Y, van Hoef V, Zhang X, Wennerberg E, Lorent J, Witt K, et al. IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells. Blood. 2016; 128: 1475-89. doi: 10.1182/blood-2016-02-698027
45. Felices M, Lenvik A, Chu S, McElmurry R, Cooley S, Tolar J, et al. Continuous IL-15 signaling leads to functional exhaustion of human natural killer cells through metabolic changes that alters their in vivo anti-tumor activity. Blood. 2016; 128(22): 551. doi: 10.1182/blood.V128.22.551.551
46. Choi I, Yoon SR, Park S-Y, Kim H, Jung S-J, Jang YJ, et al. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: A doseescalation study. Biol Blood Marrow Transplant. 2014; 20: 696-704. doi: 10.1016/j.bbmt.2014.01.031
47. Venkatasubramanian S, Cheekatla S, Paidipally P, Tripathi D, Welch E, Tvinnereim AR, et al. IL-21-dependent expansion of memory-like NK cells enhances protective immune responses against Mycobacterium tuberculosis. Mucosal Immunol. 2016; 10(4): 1-12. doi: 10.1038/mi.2016.105
48. Wendt K, Wilk E, Buyny S, Schmidt RE, Jacobs R. Interleukin-21 differentially affects human natural killer cell subsets. Immunology. 2007; 122: 486-495. doi: 10.1111/j.1365-2567.2007.02675.x
49. Strbo N, de Armas L, Liu H, Kolber MA, Lichtenheld M, Pahwa S. IL-21 augments natural killer effector functions in chronically HIV-infected individuals. AIDS. 2008; 22: 1551-1560. doi: 10.1097/QAD.0b013e3283089367
50. Li Q, Ye L-J, Ren H-L, Huyan T, Li J, Shi J-L, et al. Multiple effects of IL-21 on human NK cells in ex vivo expansion. Immunobiology. 2015; 220: 876-888. doi: 10.1016/j.imbio.2015.01.009
51. McMichael EL, Jaime-Ramirez AC, Guenterberg KD, Luedke E, Atwal LS, Campbell AR, et al. IL-21 enhances natural killer cell response to cetuximab-coated pancreatic tumor cells. Clin Cancer Res. 2017; 23: 489-502. doi: 10.1158/1078-0432.CCR-16-0004
52. Chaix J, Tessmer MS, Hoebe K, Fuseri N, Ryffel B, Dalod M, et al. Cutting edge: Priming of NK cells by IL-18. J Immunol. 2008; 181: 1627-1631. doi: 10.4049/ jimmunol.181.3.1627
53. Terrén I, Orrantia A, Astarloa-Pando G, Amarilla-Irusta A, Zenarruzabeitia O, Borrego F. Cytokine-induced memory-like NK cells: From the basics to clinical applications. Front Immunol. 2022; 13: 884648. doi: 10.3389/fimmu.2022.884648
54. Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med. 2012; 209: 2351-2365. doi: 10.1084/jem.20120944
55. Leong JW, Chase JM, Romee R, Schneider SE, Sullivan RP, Cooper MA, et al. Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on human cytokine-induced memory-like natural killer cells. Biol Blood Marrow Transplant. 2014; 20: 463-473. doi: 10.1016/j. bbmt.2014.01.006
56. Koh EK, Lee HR, Son WC, Park GY, Bae J, Park YS. Antitumor effects of NK cells expanded by activation preprocessing of autologous feeder cells before irradiation in colorectal cancer. Oncol Lett. 2023; 25(6): 232. doi: 10.3892/ol.2023.13818
57. Phan MT, Kim J, Koh SK, Lim Y, Yu H, Lee M et al. Selective expansion of NKG2C+ adaptive NK cells using K562 cells expressing HLA-E. Int J Mol Sci. 2022; 23(16): 9426. doi: 10.3390/ijms23169426
58. Ojo EO, Sharma AA, Liu R, Moreton S, Checkley-Luttge MA, Gupta K, et al. Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells. Sci Rep. 2019; 9(1): 14916. doi: 10.1038/s41598-019-51287-6
59. Hosseinzadeh F, Ai J, Ebrahimi-Barough S, Seyhoun I, Hajifathali A, Muhammadnejad S, et al. Natural killer cell expansion with autologous feeder layer and anti-CD3 antibody for immune cell therapy of hepatocellular carcinoma. Asian Pac J Cancer Prev. 2019; 20(12): 3797-3803. doi: 10.31557/APJCP.2019.20.12.3797
60. Sakamoto N, Ishikawa T, Kokura S, Okayama T, Oka K, Ideno M, et al. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. J Transl Med. 2015; 13: 277. doi: 10.1186/s12967-015-0632-8
61. Siegler U, Meyer-Monard S, Jorger S, Stern M, Tichelli A, Gratwohl A, et al. Good manufacturing practice-compliant cell sorting and large-scale expansion of single KIR-positive alloreactive human natural killer cells for multiple infusions to leukemia patients. Cytotherapy. 2010; 12: 750-763. doi: 10.3109/14653241003786155
62. Liu S, Galat V, Galat Y, Lee YKA, Wainwright D, Wu J. NK cell-based cancer immunotherapy: From basic biology to clinical development. J Hematol Oncol. 2021; 14(1): 7. doi: 10.1186/s13045-020-01014-w
63. Gómez García LM, Escudero A, Mestre C, Fuster Soler JL, Martínez AP, Vagace Valero JM, et al. Phase 2 clinical trial of infusing haploidentical K562-mb15-41BBL-activated and expanded natural killer cells as consolidation therapy for pediatric acute myeloblastic leukemia. Clin Lymphoma Myeloma Leuk. 2021; 21(5): 328-337.e1. doi: 10.1016/j.clml.2021.01.013
64. Muñoz Builes M, Vela Cuenca M, Fuster Soler JL, Astigarraga I, Pascual Martínez A, Vagace Valero JM, et al. Study protocol for a phase II, multicentre, prospective, non-randomised clinical trial to assess the safety and efficacy of infusing allogeneic activated and expanded natural killer cells as consolidation therapy for paediatric acute myeloblastic leukaemia. BMJ Open. 2020; 10(1): e029642. doi: 10.1136/bmjopen-2019-029642
65. Denman CJ, Senyukov VV, Somanchi SS, Phatarpekar PV, Kopp LM, Johnson JL, et al. Membrane-bound IL-21 promotes sustained ex vivo proliferation of human natural killer cells. PLoS One. 2012; 7: e30264. doi: 10.1371/ journal.pone.0030264
66. Hercend T, Meuer S, Reinherz EL, Schlossman SF, Ritz J. Generation of a cloned NK cell line derived from the “null cell” fraction of human peripheral blood. J Immunol. 1982; 129: 1299-1305.
67. Allan DSJ, Wu C, Mortlock RD, Chakraborty M, Rezvani K, Davidson-Moncada JK, et al. Expanded NK cells used for adoptive cell therapy maintain diverse clonality and contain long-lived memory-like NK cell populations. Mol Ther Oncolytics. 2022; 28: 74-87. doi: 10.1016/j.omto.2022.12.006
68. Granzin M, Stojanovic A, Miller M, Childs R, Huppert V, Cerwenka A. Highly efficient IL-21 and feeder cell-driven ex vivo expansion of human NK cells with therapeutic activity in a xenograft mouse model of melanoma. Oncoimmunology. 2016; 5: e1219007. doi: 10.1080/2162402X.2016. 1219007
69. Geraghty RJ, Capes-Davis A, Davis JM, Downward J, Freshney RI, Knezevic I, et al. Guidelines for the use of cell lines in biomedical research. Br J Cancer. 2014; 111(6): 1021-1046. doi: 10.1038/bjc.2014.166
70. Lee DA. Regulatory considerations for NK cells used in human immuno-therapy applications. Methods Mol Biol. 2016; 1441: 347-361. doi: 10.1007/ 978-1-4939-3684-7_29
71. North J, Bakhsh I, Marden C, Pittman H, Addison E, Navarrete C, et al. Tumor-primed human natural killer cells lyse NK-resistant tumor targets: Evidence of a two-stage process in resting NK cell activation. J Immunol. 2007; 178: 85-94. doi: 10.4049/jimmunol.178.1.85
72. Sabry M, Tsirogianni M, Bakhsh IA, North J, Sivakumaran J, Giannopoulos K, et al. Leukemic priming of resting NK cells is killer Ig-like receptorы independent but requires CD15-mediated CD2 ligation and natural cytotoxicity receptors. J Immunol. 2011; 187: 6227-6234. doi: 10.4049/ jimmunol.1101640
73. Oyer JL, Igarashi RY, Kulikowski AR, Colosimo DA, Solh MM, Zakari A, et al. Generation of highly cytotoxic natural killer cells for treatment of AML using feeder-free, particle based approach. Biol Blood Marrow Transplant. 2015; 21: 632-639. doi: 10.1016/j.bbmt.2014.12.037
74. Ferry GM, Agbuduwe C, Forrester M, Dunlop S, Chester K, Fisher J, et al. A simple and robust single-step method for CAR-Vδ1 γδT cell expansion and transduction for cancer immunotherapy. Front Immunol. 2022; 13: 863155. doi: 10.3389/fimmu.2022.863155
75. Sutlu T, Stellan B, Gilljam M, Quezada HC, Nahi H, Gahrton G, et al. Clinical-grade, large-scale, feeder-free expansion of highly active human natural killer cells for adoptive immunotherapy using an automated bioreactor. Cytotherapy. 2010; 12(8): 1044-1055. doi: 10.3109/14653249.2010.504770
76. Guan J, Wang G, Yang Q, Chen C, Deng J, Gu X, et al. Natural killer T cells in various mouse models of hepatitis. Biomed Res Int. 2021; 2021: 1782765. doi: 10.1155/2021/1782765
77. Jiang B, Wu X, Li XN, Yang X, Zhou Y, Yan H, et al. Expansion of NK cells by engineered K562 cells co-expressing 4-1BBL and mMICA, combined with soluble IL-21. Cell Immunol. 2014; 290(1): 10-20. doi: 10.1016/j.cellimm.2014.04.011
78. Goodier MR, Londei M. Lipopolysaccharide stimulates the proliferation of human CD56+CD3- NK cells: A regulatory role of monocytes and IL-10. J Immunol. 2000; 165(1): 139-147. doi: 10.4049/jimmunol.165.1.139
79. Peighambarzadeh F, Najafalizadeh A, Esmaeil N, Rezaei A, Ashrafi F, Ganjalikhani Hakemi M. Optimization of in vitro expansion and activation of human natural killer cells against breast cancer cell line. Avicenna J Med Biotechnol. 2020; 12(1): 17-23.
Рецензия
Для цитирования:
Фёдорова П.О. CAR НК-терапия: методы активации и экспансии НК-клеток. Acta Biomedica Scientifica. 2024;9(5):53-65. https://doi.org/10.29413/ABS.2024-9.5.6
For citation:
Fedorova P.O. CAR natural killer cell therapy: Natural killer cell activation and expansion. Acta Biomedica Scientifica. 2024;9(5):53-65. (In Russ.) https://doi.org/10.29413/ABS.2024-9.5.6
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