Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways

Molecular Therapy. Methods & Clinical Development
Yan YangDongfang Liu

Abstract

Clinical success of chimeric antigen receptor (CAR) T cell immunotherapy requires the engineering of autologous T cells, which limits the broader implementation of CAR cell therapy. The development of allogeneic and universal cell products will significantly broaden their application and reduce costs. Allogeneic natural killer (NK) cells can be used for universal CAR immunotherapy. Here, we develop an alternative approach for the rapid expansion of primary NK and CAR-NK cells with superior expansion capability and in vivo cytotoxicity from various sources (including peripheral blood, cord blood, and tumor tissue). We apply a human B-lymphoblastoid cell-line 721.221 (hereinafter, 221)-based artificial feeder cell system with membrane-bound interleukin 21 (mIL-21) to propagate NK and CAR-NK cells. The expansion capability, purity, and cytotoxicity of NK cells expanded with 221-mIL-21 feeder cells are superior to that of conventional K562-mIL-21 feeder cells. RNA sequencing (RNA-seq) data show that 221-mIL-21 feeder cell-expanded NK cells display a less differentiated, non-exhausted, limited fratricidal, memory-like phenotype correlated with enriched metabolic pathways, which explains underlying mechanisms. Thus, "off-the-shelf" N...Continue Reading

References

Aug 15, 1975·International Journal of Cancer. Journal International Du Cancer·R B HerbermanD H Lavrin
Aug 15, 1975·International Journal of Cancer. Journal International Du Cancer·R B HerbermanD H Lavrin
Jan 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·Y ShimizuR DeMars
Dec 1, 1995·Immunology Today·D H LynchM R Alderson
Feb 26, 2000·Annual Review of Genetics·S Nagata
Aug 12, 2006·Immunity·Nicolas AnfossiEric Vivier
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Feb 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Megan A CooperWayne M Yokoyama
Apr 23, 2009·Cancer Research·Hiroyuki FujisakiDario Campana
Jul 15, 2009·Cell·Herbert W VirginRafi Ahmed
Jan 21, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jeffrey E RubnitzWing Leung
Sep 8, 2010·Nature Reviews. Immunology·Petter Höglund, Petter Brodin
Jul 9, 2011·Nature Immunology·E John Wherry
Aug 13, 2011·The New England Journal of Medicine·David L PorterCarl H June
Sep 18, 2012·Blood·Rizwan RomeeTodd A Fehniger
Dec 5, 2012·The Journal of Experimental Medicine·Jing NiAdelheid Cerwenka
Feb 5, 2013·Journal of Immunotherapy·Sourindra N MaitiLaurence J N Cooper
Mar 23, 2013·Annual Review of Immunology·Eric O LongSumati Rajagopalan
Mar 27, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Molly P KeppelMegan A Cooper
Oct 2, 2013·Immunology Letters·Barbara Savoldo, Gianpietro Dotti
Dec 20, 2013·Oncoimmunology·Liza B JohnPhillip K Darcy
Feb 21, 2014·Science Translational Medicine·Marco L DavilaRenier Brentjens
Mar 29, 2014·The Cancer Journal·Carlos A RamosGianpietro Dotti
Sep 6, 2014·Chinese Journal of Cancer·Alan D GuerreroLaurence J N Cooper
Oct 16, 2014·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Dec 10, 2014·Cancer Immunology, Immunotherapy : CII·Monica CasucciAttilio Bondanza
Feb 26, 2015·Journal of Leukocyte Biology·Irene LisovskyNicole F Bernard
Mar 3, 2015·Frontiers in Pharmacology·Wolfgang GlienkeUlrike Koehl
Mar 10, 2015·The Journal of Allergy and Clinical Immunology·Peilin ZhengDongfang Liu
Mar 25, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nabil AhmedStephen Gottschalk

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Citations

Sep 25, 2020·Nature Communications·Hsiang-Chi TsengDongfang Liu
Oct 31, 2020·Cancers·Mireia BachillerBeatriz Martín-Antonio
Jun 3, 2021·International Journal of Molecular Sciences·Ewa WronaPiotr Potemski
Aug 10, 2021·Frontiers in Immunology·Minh Tuyet MaDongfang Liu
Sep 21, 2021·Expert Opinion on Biological Therapy·Mina HosseiniNima Rezaei

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Datasets Mentioned

BETA
AF647

Methods Mentioned

BETA
genetic modification
fluorescence-activated cell sorting
flow cytometry
confocal microscopy
xenograft
RNA-seq
flow
FACS

Software Mentioned

GenomicAlignments
STAR
FlowJo
Living Image
clusterProfiler
DESeq2
ggpubr
GSEA

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