Abstract
NK cells represent a very promising source for adoptive cellular approaches for cancer immunotherapy, and extensive research has been conducted, including clinical trials. Gene modification of NK cells can direct their specificity and enhance their function, but the efficiency of gene transfer techniques is very limited. Here we describe two protocols designed to generate mature human NK cells from gene-modified hematopoietic stem cells. These protocols use chimeric antigen receptor as the transgene, but could potentially be modified for the expression any particular transgene in human NK cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Campbell KS, Hasegawa J (2013) Natural killer cell biology: an update and future directions. J Allergy Clin Immunol 132:536–544
Childs RW, Berg M (2013) Bringing natural killer cells to the clinic: ex vivo manipulation. Hematology Am Soc Hematol Educ Program 2013:234–246
Davies JOJ, Stringaris K, Barrett JA et al (2014) Opportunities and limitations of natural killer cells as adoptive therapy for malignant disease. Cytotherapy 16:1453–1466
Leung W (2014) Infusions of allogeneic natural killer cells as cancer therapy. Clin Cancer Res 20:3390–3400
Moretta L, Montaldo E, Vacca P et al (2014) Human natural killer cells: origin, receptors, function, and clinical applications. Int Arch Allergy Immunol 164:253–264
Knorr DA, Bachanova V, Verneris MR et al (2014) Clinical utility of natural killer cells in cancer therapy and transplantation. Semin Immunol 26:161–172
Micucci F, Zingoni A, Piccoli M et al (2006) High-efficient lentiviral vector-mediated gene transfer into primary human NK cells. Exp Hematol 34:1344–1352
Shook DR, Campana D (2011) Natural killer cell engineering for cellular therapy of cancer. Tissue Antigens 78:409–415
Chu J, Deng Y, Benson DM et al (2014) CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia 28:917–927
Boissel L, Betancur M, Wels WS et al (2009) Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells. Leuk Res 33:1255–1259
Boissel L, Betancur-Boissel M, Lu W et al (2013) Retargeting NK-92 cells by means of CD19- and CD20-specific chimeric antigen receptors compares favorably with antibody-dependent cellular cytotoxicity. Oncoimmunology 2, e26527
Glienke W, Esser R, Priesner C et al (2015) Advantages and applications of CAR-expressing natural killer cells. Front Pharmacol 6:1–7
De Smedt M, Taghon T, Van de Walle I et al (2007) Notch signaling induces cytoplasmic CD3 epsilon expression in human differentiating NK cells. Blood 110:2696–2703
Luevano M, Madrigal A, Saudemont A (2012) Generation of natural killer cells from hematopoietic stem cells in vitro for immunotherapy. Cellular Mol Immunol 9:310–320
De Oliveira SN, Ryan C, Giannoni F et al (2013) Modification of hematopoietic stem/progenitor cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy. Hum Gene Ther 24:824–839
Cany J, van der Waart AB, Tordoir M et al (2013) Natural killer cells generated from cord blood hematopoietic progenitor cells efficiently target bone marrow-residing human leukemia cells in NOD/SCID/IL2Rgnull mice. PLoS One 8:1–11
Ni F, Sun R, Fu B et al (2013) IGF-1 promotes the development and cytotoxic activity of human NK cells. Nat Commun 4:1479
Cooper AR, Patel S, Senadheera S et al (2011) Highly efficient large-scale lentiviral vector concentration by tandem tangential flow filtration. J Virol Methods 177:1–9
Luevano M, Domogala A, Blundell M et al (2014) Frozen cord blood hematopoietic stem cells differentiate into higher numbers of functional natural killer cells in vitro than mobilized hematopoietic stem cells or freshly isolated cord blood hematopoietic stem cells. PLoS One 9:e87086
La Motte-mohs RN, Herer E, Zu JC (2005) Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro. In Vitro 105:1431–1439
Acknowledgment
Support was provided by the UCLA Department of Pediatrics (K-12 UCLA Child Health Research Center Development Award (CHRCDA)), Gwynne Hazen Cherry Memorial Fund, Pediatric Cancer Research Foundation, UCLA Children’s Discovery and Innovation Institute, UCLA Jonsson Comprehensive Cancer Center, UCLA/CFAR Virology Core Lab, UCLA Clinical and Translational Science Institute Grant UL1TR000124, Lights Camera Cure and St. Baldrick’s Foundation.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Lowe, E., Truscott, L.C., De Oliveira, S.N. (2016). In Vitro Generation of Human NK Cells Expressing Chimeric Antigen Receptor Through Differentiation of Gene-Modified Hematopoietic Stem Cells. In: Somanchi, S. (eds) Natural Killer Cells. Methods in Molecular Biology, vol 1441. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3684-7_20
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3684-7_20
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3682-3
Online ISBN: 978-1-4939-3684-7
eBook Packages: Springer Protocols