Artikel: CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes
2017
Abstract: T cell-mediated anti-tumor immunity plays a pivotal role in cancer immune surveillance. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a protein receptor mainly expressed in activated T cells and regulatory T cells. CTLA-4 competes with CD28 for ...
| Abstract | T cell-mediated anti-tumor immunity plays a pivotal role in cancer immune surveillance. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a protein receptor mainly expressed in activated T cells and regulatory T cells. CTLA-4 competes with CD28 for ligand binding and generates inhibitory signals to attenuate T cell activation. The blockade of CTLA-4 mediated immune inhibitory checkpoint has been associated with enhanced anti-tumor immunity. In this study, we use CRISPR-Cas9 system to knock out (KO) CTLA-4 from cytotoxic T lymphocytes (CTLs) and evaluate its effect on the anti-tumor activity of the CTLs. CTLA-4 KO CTLs robustly enhanced tumor cell death by 40% compared to the control and facilitated apoptosis and caspase activities in tumor cells. The knockout of CTLA-4 also increased TNF-α and IFN-γ secretion of the CTLs by approximately 2-fold. The effectiveness of CTLA-4 KO in enhancing anti-tumor activity of the CTLs was verified in vivo using mouse xenograft model. The xenografted mice treated with CTLA-4 KO CTLs demonstrated repressed tumor growth and prolonged survival compared to the control group. Our data suggest that CRISPR targeting CTLA-4 immune checkpoint could significantly improve the anti-tumor activity of CTLs. |
|||||
|---|---|---|---|---|---|---|
| Schlagwörter | antineoplastic activity ; apoptosis ; caspases ; cytotoxic T-lymphocytes ; cytotoxicity ; enzyme activity ; genetic engineering ; immunity ; interferon-gamma ; ligands ; mice ; models ; monitoring ; neoplasm cells ; neoplasms ; secretion ; tumor necrosis factor-alpha | |||||
| Sprache | Englisch | |||||
| Erscheinungsverlauf | 2017-1215 | |||||
| Umfang | p. 36-41. | |||||
| Erscheinungsort | Elsevier B.V. | |||||
| Dokumenttyp | Artikel | |||||
| ZDB-ID | 391792-7 | |||||
| ISSN | 1879-0038 ; 0378-1119 | |||||
| ISSN (online) | 1879-0038 | |||||
| ISSN | 0378-1119 | |||||
| DOI | 10.1016/j.gene.2017.09.010 | |||||
| Signatur |
|
|||||
| Datenquelle | NAL Katalog (AGRICOLA) |
Volltext online
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Bonn
| Z 79/715: Hefte anzeigen |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.
Fernleihe an ZB MED
Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.