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Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells

Ojo, Evelyn O ; Sharma, Ashish Arunkumar ; Liu, Ruifu ; Moreton, Stephen ; Checkley-Luttge, Mary-Ann ; Gupta, Kalpana ; Lee, Grace ; Lee, Dean A ; Otegbeye, Folashade ; Sekaly, Rafick-Pierre ; de Lima, Marcos ; Wald, David N

Scientific reports, 2019-10, Vol.9 (1), p.14916-12, Article 14916 [Periódico revisado por pares]

England: Nature Publishing Group

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Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells
Autor: Ojo, Evelyn O ; Sharma, Ashish Arunkumar ; Liu, Ruifu ; Moreton, Stephen ; Checkley-Luttge, Mary-Ann ; Gupta, Kalpana ; Lee, Grace ; Lee, Dean A ; Otegbeye, Folashade ; Sekaly, Rafick-Pierre ; de Lima, Marcos ; Wald, David N
Assuntos: Animal models ; Animals ; c-Myc protein ; Cell activation ; Cell Line, Tumor ; Cell Membrane - immunology ; Cell Membrane - metabolism ; Cell Proliferation ; Coculture Techniques ; Cytotoxicity ; Feeder Cells - metabolism ; Glycolysis ; Healthy Volunteers ; Humans ; Immunotherapy - methods ; Interleukin 2 ; Interleukin 21 ; Interleukins - immunology ; Interleukins - metabolism ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Killer Cells, Natural - transplantation ; Lymphocytes T ; Metabolic activation ; Metabolic rate ; Mice ; Myc protein ; Natural killer cells ; Neoplasms - immunology ; Neoplasms - therapy ; Primary Cell Culture - methods ; Sarcoma ; Solid tumors ; Stat3 protein ; Tumor cells ; Xenograft Model Antitumor Assays
É parte de: Scientific reports, 2019-10, Vol.9 (1), p.14916-12, Article 14916
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SourceType-Scholarly Journals-1
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Descrição: NK cell adoptive therapy is a promising cancer therapeutic approach, but there are significant challenges that limiting its feasibility and clinical efficacy. One difficulty is the paucity of clinical grade manufacturing platforms to support the large scale expansion of highly active NK cells. We created an NK cell feeder cell line termed 'NKF' through overexpressing membrane bound IL-21 that is capable of inducing robust and sustained proliferation (>10,000-fold expansion at 5 weeks) of highly cytotoxic NK cells. The expanded NK cells exhibit increased cytotoxic function against a panel of blood cancer and solid tumor cells as compared to IL-2-activated non-expanded NK cells. The NKF-expanded NK cells also demonstrate efficacy in mouse models of human sarcoma and T cell leukemia. Mechanistic studies revealed that membrane-bound IL-21 leads to an activation of a STAT3/c-Myc pathway and increased NK cell metabolism with a shift towards aerobic glycolysis. The NKF feeder cell line is a promising new platform that enables the large scale proliferation of highly active NK cells in support of large scale third party NK cell clinical studies that have been recently intiatied. These results also provide mechanistic insights into how membrane-bound IL-21 regulates NK cell expansion.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells

Ojo, Evelyn O ; Sharma, Ashish Arunkumar ; Liu, Ruifu ; Moreton, Stephen ; Checkley-Luttge, Mary-Ann ; Gupta, Kalpana ; Lee, Grace ; Lee, Dean A ; Otegbeye, Folashade ; Sekaly, Rafick-Pierre ; de Lima, Marcos ; Wald, David N

England: Nature Publishing Group

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