Engineering light-controllable CAR T cells for cancer immunotherapy.
Animals
Antigens, CD19
/ immunology
Antigens, Neoplasm
/ immunology
Calcium-Binding Proteins
/ genetics
Cell Line
Cryptochromes
/ genetics
Cytotoxicity, Immunologic
/ immunology
Humans
Immunotherapy, Adoptive
/ methods
Light
Lymphocyte Activation
/ genetics
Mice
Models, Biological
Neoplasms
/ immunology
Protein Binding
Protein Multimerization
Receptors, Chimeric Antigen
/ genetics
T-Lymphocytes
/ immunology
Transcriptional Activation
/ radiation effects
Xenograft Model Antitumor Assays
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
30
07
2019
accepted:
03
12
2019
entrez:
5
3
2020
pubmed:
5
3
2020
medline:
23
10
2020
Statut:
epublish
Résumé
T cells engineered to express chimeric antigen receptors (CARs) can recognize and engage with target cancer cells with redirected specificity for cancer immunotherapy. However, there is a lack of ideal CARs for solid tumor antigens, which may lead to severe adverse effects. Here, we developed a light-inducible nuclear translocation and dimerization (LINTAD) system for gene regulation to control CAR T activation. We first demonstrated light-controllable gene expression and functional modulation in human embryonic kidney 293T and Jurkat T cell lines. We then improved the LINTAD system to achieve optimal efficiency in primary human T cells. The results showed that pulsed light stimulations can activate LINTAD CAR T cells with strong cytotoxicity against target cancer cells, both in vitro and in vivo. Therefore, our LINTAD system can serve as an efficient tool to noninvasively control gene activation and activate inducible CAR T cells for precision cancer immunotherapy.
Identifiants
pubmed: 32128416
doi: 10.1126/sciadv.aay9209
pii: aay9209
pmc: PMC7030928
doi:
Substances chimiques
Antigens, CD19
0
Antigens, Neoplasm
0
CD19 molecule, human
0
CIB1 protein, human
0
CRY2 protein, human
0
Calcium-Binding Proteins
0
Cryptochromes
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaay9209Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM126016
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM125379
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA238042
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA204704
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL121365
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA209629
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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