Reducing Ex Vivo Culture Improves the Antileukemic Activity of Chimeric Antigen Receptor (CAR) T Cells.

Cancer Immunology Research
Saba GhassemiMichael C Milone

Abstract

The success of chimeric antigen receptor (CAR)-mediated immunotherapy in acute lymphoblastic leukemia (ALL) highlights the potential of T-cell therapies with directed cytotoxicity against specific tumor antigens. The efficacy of CAR T-cell therapy depends on the engraftment and persistence of T cells following adoptive transfer. Most protocols for T-cell engineering routinely expand T cells ex vivo for 9 to 14 days. Because the potential for engraftment and persistence is related to the state of T-cell differentiation, we hypothesized that reducing the duration of ex vivo culture would limit differentiation and enhance the efficacy of CAR T-cell therapy. We demonstrated that T cells with a CAR-targeting CD19 (CART19) exhibited less differentiation and enhanced effector function in vitro when harvested from cultures at earlier (day 3 or 5) compared with later (day 9) timepoints. We then compared the therapeutic potential of early versus late harvested CART19 in a murine xenograft model of ALL and showed that the antileukemic activity inversely correlated with ex vivo culture time: day 3 harvested cells showed robust tumor control despite using a 6-fold lower dose of CART19, whereas day 9 cells failed to control leukemia at limit...Continue Reading

References

Feb 15, 2001·Human Gene Therapy·UNKNOWN Guidance for Industry, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Eval
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elisabetta ParrettaFrancesca Di Rosa
Jun 28, 2005·Proceedings of the National Academy of Sciences of the United States of America·Christopher A KlebanoffNicholas P Restifo
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gayle PulleTania H Watts
Dec 7, 2007·The Journal of Clinical Investigation·Carolina BergerStanley R Riddell
Feb 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Carmine CarpenitoCarl H June
Apr 23, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Michael C MiloneCarl H June
Jun 16, 2009·Nature Medicine·Luca GattinoniNicholas P Restifo
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Christian S HinrichsNicholas P Restifo
Feb 2, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paul F RobbinsSteven A Rosenberg
Aug 13, 2011·The New England Journal of Medicine·David L PorterCarl H June
Sep 20, 2011·Nature Medicine·Luca GattinoniNicholas P Restifo
Oct 21, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sujatha MuralidharanGianpietro Dotti
Jun 27, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Roddy S O'ConnorMichael C Milone
Sep 22, 2012·Nature Reviews. Cancer·Luca GattinoniNicholas P Restifo
Mar 27, 2013·The New England Journal of Medicine·Stephan A GruppCarl H June
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ali ZaidScott N Mueller
Oct 16, 2014·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Dec 15, 2015·The Journal of Clinical Investigation·Christopher A KlebanoffNicholas P Restifo
Dec 15, 2015·Science Translational Medicine·Giacomo OliveiraChiara Bonini
Jan 8, 2016·Science Translational Medicine·Nathan SinghDavid M Barrett
Aug 24, 2016·Nature Reviews. Cancer·Andrew D FesnakBruce L Levine
Nov 30, 2016·Human Gene Therapy Methods·Tangying Lily LuSteven A Feldman
Dec 29, 2016·The New England Journal of Medicine·Christine E BrownBehnam Badie
Mar 16, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James N KochenderferSteven A Rosenberg
May 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael Schmueck-HenneresseCliona M Rooney
Jun 13, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Andras HeczeyMalcolm K Brenner
Jun 18, 2017·Science·Jennifer Couzin-Frankel

❮ Previous
Next ❯

Citations

Jan 5, 2019·Current Opinion in HIV and AIDS·Chantelle L Ahlenstiel, Stuart G Turville
Feb 9, 2019·Human Vaccines & Immunotherapeutics·January Salas-MckeeJoseph A Fraietta
Jan 27, 2019·American Journal of Hematology·Steven FeinsJoseph A Fraietta
Dec 12, 2018·Annual Review of Immunology·Sonia GuedanCarl H June
Apr 16, 2019·Expert Opinion on Biological Therapy·Isabelle MagalhaesSofia Berglund
Jul 18, 2019·Critical Reviews in Clinical Laboratory Sciences·Mansour PoorebrahimAngel Cid-Arregui
Jul 30, 2019·Immunological Reviews·David AkhavanChristine E Brown
Oct 5, 2019·Human Vaccines & Immunotherapeutics·Jan David BeckMustafa Diken
Oct 3, 2019·Current Opinion in Hematology·Xiaoqing Li, Weihong Chen
Jun 28, 2020·Biotechnology Journal·Elena CostariolQasim A Rafiq
Aug 17, 2020·Journal of Immunotherapy·Vandana KeskarSteven L Highfill
Sep 15, 2020·Current Opinion in Hematology·Ofrat Beyar-Katz, Saar Gill
Mar 2, 2019·Nature Reviews. Immunology·David O'SullivanErika L Pearce
Aug 9, 2019·Journal of Translational Medicine·Claire CoeshottBrian Nankervis
Dec 1, 2019·BMC Biotechnology·Noah H RichardsonMarko Radic
May 5, 2020·Oncoimmunology·Luiza de Macedo AbdoMartín Hernán Bonamino
Aug 23, 2020·Cancers·Leonardo ChicaybamBryan E Strauss
Dec 19, 2018·Frontiers in Immunology·Kristen B LongJoseph A Fraietta
Apr 26, 2020·Clinical and Experimental Medicine·Stefan LundhJoseph A Fraietta
Aug 28, 2020·Frontiers in Immunology·Zachary JacksonJane S Reese
Mar 3, 2019·Scientific Reports·Justin A JarrellRyan S Pawell
May 28, 2019·Frontiers in Immunology·Marjolein SchluckJorieke Weiden
Aug 1, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Lorraine SpringuelFrédéric F Lehmann
Jul 30, 2020·Cancers·Andriy ZhylkoAgnieszka Graczyk-Jarzynka
Nov 22, 2019·Paediatric Drugs·Holly L PacentaSamuel John
Nov 1, 2018·Advances in Cell and Gene Therapy·Karlo PericaRenier J Brentjens
Oct 22, 2020·Scientific Reports·Mateusz P PoltorakLothar Germeroth
Dec 1, 2020·Platelets·Lassina BarroThierry Burnouf
Jun 21, 2020·Cancer Research·Hannah M KnochelmannChrystal M Paulos
Nov 2, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adam D CohenMadhav V Dhodapkar
Oct 2, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eduardo HuartePaul A Smith
Dec 9, 2020·Cancer Letters·Hosein RostamianHamid R Mirzaei
Nov 11, 2019·Trends in Cancer·Matthew T WitkowskiIannis Aifantis
Jan 27, 2021·Blood Advances·Marion Subklewe
Jan 26, 2021·Frontiers in Oncology·Jiaqiao FanJianxun Song
Aug 21, 2020·The Journal of Clinical Investigation·Jinmin LeeAimee S Payne
Nov 24, 2020·Journal of Cellular and Molecular Medicine·Li-Rong YangZong-Liu Hou

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