Identifying the optimal donor for natural killer cell adoptive therapy to treat paediatric B- and T-cell acute lymphoblastic leukaemia

Clinical & Translational Immunology
Bree FoleyJason Waithman

Abstract

Natural killer (NK) cells are an attractive source of cells for an 'off the shelf' cellular therapy because of their innate capacity to target malignant cells, and ability to be transferred between donors and patients. However, since not all NK cells are equally effective at targeting cancer, selecting the right donor for cellular therapy is critical for the success of the treatment. Recently, cellular therapies utilising NK cells from cytomegalovirus (CMV)-seropositive donors have been explored. However, whether these NK cells are the best source to treat paediatric acute lymphoblastic leukaemia (ALL) remains unclear. Using a panel of patient-derived paediatric B- and T-ALL, we assessed the ability of NK cells from 49 healthy donors to mount an effective functional response against these two major subtypes of ALL. From this cohort, we have identified a pool of donors with superior activity against multiple ALL cells. While these donors were more likely to be CMV+, we identified multiple CMVneg donors within this group. Furthermore, NK cells from these donors recognised B- and T-ALL through different activating receptors. Dividing functional NK cells into 29 unique subsets, we observed that within each individual the same NK ce...Continue Reading

References

Jan 1, 1996·Annual Review of Immunology·A MorettaL Moretta
May 23, 1998·Annual Review of Immunology·L L Lanier
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wing LeungRupert Handgretinger
Jan 13, 2009·Nature·Joseph C SunLewis L Lanier
Feb 9, 2010·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Robert GodalJeffrey S Miller
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sandra Lopez-VergèsLewis L Lanier
Sep 8, 2012·Current Opinion in Hematology·Andrea Velardi
Oct 19, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bree FoleyJeffrey S Miller
Dec 25, 2013·Frontiers in Immunology·Carolyn M NielsenEleanor M Riley
Oct 21, 2014·PLoS Pathogens·Merlin Luetke-EverslohChiara Romagnani
Jun 24, 2017·Cancer Immunology Research·Lisa L LiuKarl-Johan Malmberg
Aug 10, 2017·Cancer Research·Frank CichockiJeffrey S Miller
Feb 1, 2018·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Jan 25, 2019·JCI Insight·Frank CichockiJeffrey S Miller

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Citations

Nov 27, 2020·International Journal of Molecular Sciences·Samantha BarnesBree Foley

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Methods Mentioned

BETA
flow cytometry

Clinical Trials Mentioned

NCT03081780
NCT03319459

Software Mentioned

GraphPad
Prism
FlowJo

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