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

Abstract：

: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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ojo EO,Sharma AA,Liu R,Moreton S,Checkley-Luttge MA,Gupta K,Lee G,Lee DA,Otegbeye F,Sekaly RP,de Lima M,Wald DN

doi

10.1038/s41598-019-51287-6

subject

Has Abstract

pub_date

2019-10-17 00:00:00

pages

14916

issue

1

issn

2045-2322

pii

10.1038/s41598-019-51287-6

journal_volume

9

pub_type

杂志文章

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