CAR T cells: Building on the CD19 paradigm

Spearheaded by the therapeutic use of chimeric antigen receptors (CARs) targeting CD19, synthetic immunology has entered the clinical arena. CARs are recombinant receptors for antigen that engage cell surface molecules through the variable region of an antibody and signal through arrayed T‐cell acti...

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Published inEuropean journal of immunology Vol. 51; no. 9; pp. 2151 - 2163
Main Authors Globerson Levin, Anat, Rivière, Isabelle, Eshhar, Zelig, Sadelain, Michel
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 01.09.2021
Subjects
Antigens
Autoimmunity
Cancer immunotherapy
CD19
CD19 antigen
Cell surface
Chimeric antigen receptor (CAR) T cell
Chimeric antigen receptors
Cytotoxicity
Genome editing
Genomes
Immunotherapy
Lymphocytes
Lymphocytes T
Macrophages
Major histocompatibility complex
Natural killer cells
Pluripotency
Senescence
Solid tumors
Stem cells
Tumor immunology
Variable region
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Summary:Spearheaded by the therapeutic use of chimeric antigen receptors (CARs) targeting CD19, synthetic immunology has entered the clinical arena. CARs are recombinant receptors for antigen that engage cell surface molecules through the variable region of an antibody and signal through arrayed T‐cell activating and costimulatory domains. CARs allow redirection of T‐cell cytotoxicity against any antigen of choice, independent of MHC expression. Patient T cells engineered to express CARs specific for CD19 have yielded remarkable outcomes in subjects with relapsed/refractory B‐ cell malignancies, setting off unprecedented interest in T‐cell engineering and cell‐based cancer immunotherapy. In this review, we present the challenges to extend the use of CAR T cells to solid tumors and other pathologies. We further highlight progress in CAR design, cell manufacturing, and genome editing, which in aggregate hold the promise of generating safer and more effective genetically instructed immunity. Novel engineered cell types, including innate T‐cell types, natural killer (NK) cells, macrophages, and induced pluripotent stem cell‐derived immune cells, are on the horizon, as are applications of CAR T cells to treat autoimmunity, severe infections, and senescence‐associated pathologies.
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ISSN:0014-2980
1521-4141
1521-4141
DOI:10.1002/eji.202049064