T cell engineered with a novel nanobody-based chimeric antigen receptor against VEGFR2 as a candidate for tumor immunotherapy.
IUBMB Life
; 71(9): 1259-1267, 2019 09.
Article
in En
| MEDLINE
| ID: mdl-30724452
ABSTRACT
Solid tumors that are responsible for more than 85% of cancer death cases need angiogenesis for their growth and metastasis. Among antiangiogenic therapies, targeting the vascular endothelial growth factor receptor 2 (VEGFR2) that is over-expressed on tumor vasculatures has been a promising strategy. In this study, we developed a second generation nanobody (VHH)-based CAR T cell targeting VEGFR2-expressing tumor cells. The CAR T cell was developed by linking the anti-VEGFR2 VHH to a spacer, and signaling domains of CD28 and CD3 ζ. The T cells were activated with anti-CD3 plus rIL-2 and electroporated with a plasmid encoding the CAR construct. The expression of activation markers, CD69 and CD25, on CAR T cells upon coculturing with VEGFR2-expressing cells were 41% and 48%, and the IL-2 and IFN-γ production were 470 pg/mL and 360 pg/mL, respectively. The expression of degranulation marker, CD107a, was 30% and the cytotoxic activity of the CAR T cells reached to more than 30% with ET ratio of 91. The anti-VEGFR2 CAR but not mock T cells mediated specific lysis of 293-KDR cells expressing human VEGFR2 and might be considered as a candidate for adoptive T-cell immunotherapy of solid tumors. © 2019 IUBMB Life, 71(9)1259-1267, 2019.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vascular Endothelial Growth Factor Receptor-2
/
Single-Domain Antibodies
/
Receptors, Chimeric Antigen
/
Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
IUBMB Life
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2019
Document type:
Article
Affiliation country:
Irán