Depletion of T cells
Adoptive Transfer
/ adverse effects
Animals
Caspase 9
/ biosynthesis
Cell Death
Cell Line
Coculture Techniques
Cytokines
/ metabolism
Cytotoxicity, Immunologic
DNA-Binding Proteins
/ genetics
Disease Models, Animal
Enzyme Induction
Female
Hepatitis B Antigens
/ immunology
Hepatitis B virus
/ immunology
Hepatitis B, Chronic
/ immunology
Humans
Interleukin Receptor Common gamma Subunit
/ genetics
Male
Mice, Inbred C57BL
Mice, Knockout
Receptors, Chimeric Antigen
/ genetics
Simplexvirus
/ enzymology
T-Lymphocytes
/ enzymology
Thymidine Kinase
/ genetics
Transduction, Genetic
T-cell therapy
chimeric antigen receptor (CAR)
chronic hepatitis B
inducible caspase 9
safeguard molecules
suicide switch
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
30
06
2021
accepted:
17
09
2021
entrez:
25
10
2021
pubmed:
26
10
2021
medline:
24
12
2021
Statut:
epublish
Résumé
T-cell therapy with T cells that are re-directed to hepatitis B virus (HBV)-infected cells by virus-specific receptors is a promising therapeutic approach for treatment of chronic hepatitis B and HBV-associated cancer. Due to the high number of target cells, however, side effects such as cytokine release syndrome or hepatotoxicity may limit safety. A safeguard mechanism, which allows depletion of transferred T cells on demand, would thus be an interesting means to increase confidence in this approach. In this study, T cells were generated by retroviral transduction to express either an HBV-specific chimeric antigen receptor (S-CAR) or T-cell receptor (TCR), and in addition either inducible caspase 9 (iC9) or herpes simplex virus thymidine kinase (HSV-TK) as a safety switch. Real-time cytotoxicity assays using HBV-replicating hepatoma cells as targets revealed that activation of both safety switches stopped cytotoxicity of S-CAR- or TCR-transduced T cells within less than one hour.
Identifiants
pubmed: 34691041
doi: 10.3389/fimmu.2021.734246
pmc: PMC8527178
doi:
Substances chimiques
Cytokines
0
DNA-Binding Proteins
0
Hepatitis B Antigens
0
Il2rg protein, mouse
0
Interleukin Receptor Common gamma Subunit
0
Rag2 protein, mouse
0
Receptors, Chimeric Antigen
0
Thymidine Kinase
EC 2.7.1.21
CASP9 protein, human
EC 3.4.22.-
Caspase 9
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
734246Informations de copyright
Copyright © 2021 Klopp, Schreiber, Kosinska, Pulé, Protzer and Wisskirchen.
Déclaration de conflit d'intérêts
KW and UP are co-founders and shareholders of SCG Cell Therapy Pte. Ltd. KW is partially employed by SCG Cell Therapy GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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