Development and characterisation of NKp44-based chimeric antigen receptors that confer T cells with NK cell-like specificity

Clinical & Translational Immunology
Yasushi KasaharaChihaya Imai

Abstract

One of the reasons as to why chimeric antigen receptors (CAR)-T cell therapy for malignancies other than CD19- or BCMA-positive tumors has yet to produce remarkable progress is the paucity of targetable antigens. NKp44 is only expressed by activated natural killer cells and detects a variety of transformed cells, while it reportedly does not react with normal tissues. The aim of this study is to develop CAR-T cell that can target multiple types of tumor cells. We created a series of novel CAR constructs in first-generation (1G) and second-generation (2G) CAR format with the extracellular immunoglobulin-like domain of NKp44 (NKp44-CAR). Transduction of the best 1G construct into human primary T cells led to specific cytotoxic effects and cytokine secretion upon encountering multiple types of neoplastic cells including AML, T-ALL and childhood solid tumors. Replacement of the extracellular hinge domain of NKp44 with that of CD8α resulted in diminished CAR function. The 1G NKp44-CAR-T cells exhibited significantly better tumor control in long-term co-culture assays compared with activated NK cells, as well as with NK cells transduced with identical NKp44-CAR. T cells transduced with the best 2G-CAR construct with 4-1BB co-stimulat...Continue Reading

References

Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kerry S CampbellTracey L Catina
Feb 7, 2009·Journal of Proteome Research·Marie-Lyn HechtPeter H Seeberger
Jul 29, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Oren HershkovitzAngel Porgador
Feb 25, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Richard A MorganSteven A Rosenberg
Mar 23, 2010·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Michael C JensenStephen J Forman
Jun 23, 2010·Immunology and Cell Biology·Hollie J PegramMichael H Kershaw
Jan 8, 2011·Science·Eric VivierSophie Ugolini
Oct 25, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Benyamin RosentalAngel Porgador
Mar 23, 2012·Nature Reviews. Immunology·Eric VivierLaurent Brossay
Aug 2, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tong ZhangCharles L Sentman
Feb 19, 2013·Trends in Immunology·Joachim KochOfer Mandelboim
Aug 21, 2013·Blood·Florence BaychelierVincent Vieillard
Dec 18, 2013·Science Translational Medicine·Victor D FedorovMichel Sadelain
Feb 4, 2014·Journal of Immunological Methods·Janet Kerstin PeperStefan Stevanović
Oct 16, 2014·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Mar 25, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nabil AhmedStephen Gottschalk
Apr 9, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Steven C KatzRichard P Junghans
Jan 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·David T RodgersTravis S Young
Dec 29, 2016·The New England Journal of Medicine·Christine E BrownBehnam Badie
Mar 16, 2017·Journal of Hematology & Oncology·Le QinPeng Li
Dec 26, 2017·Cell·Alexander D BarrowMarco Colonna
Feb 1, 2018·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
May 31, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jennifer N BrudnoJames N Kochenderfer
Sep 20, 2018·Oncoimmunology·Silvia GaggeroClaudia Cantoni
Nov 24, 2018·Frontiers in Immunology·Andrea Schmidts, Marcela V Maus
Apr 24, 2019·Nature Medicine·Zhitao YingSi-Yi Chen
May 3, 2019·The New England Journal of Medicine·Noopur RajeJames N Kochenderfer

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Citations

Oct 15, 2020·International Journal of Molecular Sciences·Nicholas J ChandlerMatthew E Call

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Methods Mentioned

BETA
flow cytometry
ELISA
genetic modification
xenograft
PCR
transfect

Software Mentioned

EZR
iCELLigence

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