Emerging Approaches for Regulation and Control of CAR T Cells: A Mini Review

Lærke J B Brandt; Mike B Barnkob; Yale S Michaels; Julia Heiselberg; Torben Barington

doi:10.3389/fimmu.2020.00326

Emerging Approaches for Regulation and Control of CAR T Cells: A Mini Review

Front Immunol. 2020 Feb 26:11:326. doi: 10.3389/fimmu.2020.00326. eCollection 2020.

Authors

Lærke J B Brandt¹, Mike B Barnkob¹, Yale S Michaels², Julia Heiselberg¹, Torben Barington¹

Affiliations

¹ Department of Clinical Immunology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
² School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada.

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.

Publication types

Review

MeSH terms

Antigens, Neoplasm / immunology
CRISPR-Cas Systems
Cell Hypoxia
Cetuximab / pharmacology
Cetuximab / therapeutic use
Cytokine Release Syndrome / etiology
Cytokine Release Syndrome / prevention & control*
Cytokines / biosynthesis
Genes, Transgenic, Suicide
Humans
Immunotherapy, Adoptive* / adverse effects
Immunotherapy, Adoptive* / methods
Interleukin 1 Receptor Antagonist Protein / biosynthesis
Lymphocyte Activation
Protease Inhibitors / pharmacology
Protease Inhibitors / therapeutic use
Protein Binding
Protein Domains
Receptors, Antigen, T-Cell, alpha-beta / genetics
Receptors, Chimeric Antigen / genetics
Receptors, Chimeric Antigen / immunology
Rituximab / pharmacology
Rituximab / therapeutic use
T-Cell Antigen Receptor Specificity
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / transplantation
Tetracycline / pharmacology
Transcription, Genetic / drug effects
Transfection
Tumor Microenvironment

Substances

Antigens, Neoplasm
Cytokines
Il1rn protein, mouse
Interleukin 1 Receptor Antagonist Protein
Protease Inhibitors
Receptors, Antigen, T-Cell, alpha-beta
Receptors, Chimeric Antigen
Rituximab
Tetracycline
Cetuximab