Abstract
Chimeric antigen receptor (CAR) T cells have emerged as a promising treatment for patients with advanced B-cell cancers. However, widespread application of the therapy is currently limited by potentially life-threatening toxicities due to a lack of control of the highly potent transfused cells. Researchers have therefore developed several regulatory mechanisms in order to control CAR T cells in vivo. Clinical adoption of these control systems will depend on several factors, including the need for temporal and spatial control, the immunogenicity of the requisite components as well as whether the system allows reversible control or induces permanent elimination. Here we describe currently available and emerging control methods and review their function, advantages, and limitations.
Keywords:
T cell; cancer; cell therapy; chimeric antigen receptor; immunotherapy; regulation; synthetic.
Copyright © 2020 Brandt, Barnkob, Michaels, Heiselberg and Barington.
MeSH terms
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Antigens, Neoplasm / immunology
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CRISPR-Cas Systems
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Cell Hypoxia
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Cetuximab / pharmacology
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Cetuximab / therapeutic use
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Cytokine Release Syndrome / etiology
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Cytokine Release Syndrome / prevention & control*
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Cytokines / biosynthesis
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Genes, Transgenic, Suicide
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Humans
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Immunotherapy, Adoptive* / adverse effects
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Immunotherapy, Adoptive* / methods
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Interleukin 1 Receptor Antagonist Protein / biosynthesis
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Lymphocyte Activation
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Protease Inhibitors / pharmacology
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Protease Inhibitors / therapeutic use
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Protein Binding
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Protein Domains
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Chimeric Antigen / genetics
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Receptors, Chimeric Antigen / immunology
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Rituximab / pharmacology
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Rituximab / therapeutic use
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T-Cell Antigen Receptor Specificity
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / transplantation
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Tetracycline / pharmacology
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Transcription, Genetic / drug effects
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Transfection
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Tumor Microenvironment
Substances
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Antigens, Neoplasm
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Cytokines
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Il1rn protein, mouse
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Interleukin 1 Receptor Antagonist Protein
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Protease Inhibitors
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Chimeric Antigen
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Rituximab
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Tetracycline
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Cetuximab