CD19 chimeric antigen receptor T cell therapy for haematological malignancies

British Journal of Haematology
Sara GhorashianPersis Amrolia

Abstract

T cells can be redirected to recognize tumour antigens by genetic modification to express a chimeric antigen receptor (CAR). These consist of antibody-derived antigen-binding regions linked to T cell signalling elements. CD19 is an ideal target because it is expressed on most B cell malignancies as well as normal B cells but not on other cell types, restricting any 'on target, off tumour' toxicity to B cell depletion. Recent clinical studies involving CD19 CAR-directed T cells have shown unprecedented responses in a range of B cell malignancies, even in patients with chemorefractory relapse. Durable responses have been achieved, although the persistence of modified T cells may be limited. This therapy is not without toxicity, however. Cytokine release syndrome and neurotoxicity appear to be frequent but are treatable and reversible. CAR T cell therapy holds the promise of a tailored cellular therapy, which can form memory and be adapted to the tumour microenvironment. This review will provide a perspective on the currently available data, as well as on future developments in the field.

References

Dec 10, 2002·Annual Review of Immunology·Ronald H Schwartz
Apr 3, 2003·Immunological Reviews·Leonard J Appleman, Vassiliki A Boussiotis
Jul 10, 2003·Cytotherapy·M PuleA Lawson
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Helene M FinneyAlastair D G Lawson
Feb 25, 2005·Blood·Karin C StraathofCliona M Rooney
Feb 25, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul A AntonyNicholas P Restifo
Jun 28, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Martin A PulèMalcolm K Brenner
Sep 15, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Renier J BrentjensMichel Sadelain
Dec 7, 2007·The Journal of Clinical Investigation·Carolina BergerStanley R Riddell
May 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Scott E JamesOliver W Press
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 30, 2009·Journal of Immunotherapy·James N KochenderferSteven A Rosenberg
Jan 22, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eleanor J CheadleDavid E Gilham
Mar 23, 2010·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Michael C JensenStephen J Forman
Apr 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yvonne Y ChenChristina D Smolke
Apr 19, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Steven A RosenbergMark E Dudley
May 5, 2011·The Journal of Clinical Investigation·Barbara SavoldoGianpietro Dotti
Jul 5, 2011·Nature Chemical Biology·Kimberly M BongerThomas J Wandless
Aug 13, 2011·The New England Journal of Medicine·David L PorterCarl H June
Sep 20, 2011·Nature Medicine·Luca GattinoniNicholas P Restifo
Nov 4, 2011·The New England Journal of Medicine·Antonio Di StasiMalcolm K Brenner

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Citations

Nov 20, 2015·Expert Review of Hematology·Benjamin KasendaIan Chau
Mar 24, 2016·Journal of Cellular and Molecular Medicine·Annette RomanskiTorsten Tonn
Aug 1, 2015·Molecular Cancer·Antonio PalumboLuiz Eurico Nasciutti
Mar 25, 2016·Expert Review of Hematology·Elena MainoRenato Bassan
May 22, 2016·Blood·Jennifer N Brudno, James N Kochenderfer
Apr 11, 2017·Acta Pharmacologica Sinica·Lan-Lan ZhangJi-Long Chen
Jan 22, 2020·Journal of the American Heart Association·Michael A BiersmithDaniel Addison
Jul 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Peng-Fei ZhangWei Wang
May 5, 2018·Journal of Immunology Research·Jeffrey KouryAndrew Tran
May 18, 2018·Molecular Cancer·Yanyu PangGuan Jiang
Nov 25, 2018·Virchows Archiv : an International Journal of Pathology·Maartje W RohaanJohn B A G Haanen
Apr 25, 2017·Journal of Hematology & Oncology·Annie Im, Steven Z Pavletic
Nov 3, 2020·Therapeutic Advances in Medical Oncology·Qing CaiZhaoming Li
Jan 27, 2020·Trends in Biotechnology·Enrico FritscheMohamed Abou-El-Enein
Mar 7, 2021·International Journal of Molecular Sciences·Wan-Tai WuYi-Yen Lee
Sep 10, 2021·Immunotherapy·Essam A TawfikNada M Zaidan

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