Anti-tumor effects of vascular endothelial growth factor/vascular endothelial growth factor receptor binding domain-modified chimeric antigen receptor T cells.
Cytotherapy
; 23(9): 810-819, 2021 09.
Article
in En
| MEDLINE
| ID: mdl-34244079
ABSTRACT
BACKGROUND AIMS:
The vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) signaling pathway plays an important role in angiogenesis and lymphangiogenesis, which are closely related to tumor cell growth, survival, tissue infiltration and metastasis. Blocking/interfering with the interaction between VEGF and VEGFR to inhibit angiogenesis/lymphangiogenesis has become an important means of tumor therapy.METHODS:
Here the authors designed a novel chimeric antigen receptor (CAR) lentiviral vector expressing the VEGF-C domain targeting both VEGFR-2 and VEGFR-3 (VEGFR-2/3 CAR) and then transduced CD3-positive T cells with VEGFR-2/3 CAR lentivirus.RESULTS:
After co-culturing with target cells, VEGFR-2/3 CAR T cells showed potent cytotoxicity against both VEGFR-2- and VEGFR-3-positive breast cancer cells, with increased simultaneous secretion of interferon gamma, tumor necrosis factor alpha and interleukin-2 cytokines. Moreover, CAR T cells were able to destroy the tubular structures formed by human umbilical vein endothelial cells and significantly inhibit the growth, infiltration and metastasis of orthotopic mammary xenograft tumors in a female BALB/c nude mice model.CONCLUSIONS:
The authors' results indicate that VEGFR-2/3 CAR T cells targeting both VEGFR-2 and VEGFR-3 have significant anti-tumor activity, which expands the application of conventional CAR T-cell therapy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vascular Endothelial Growth Factor Receptor-3
/
Vascular Endothelial Growth Factor A
/
Receptors, Chimeric Antigen
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Cytotherapy
Journal subject:
TERAPEUTICA
Year:
2021
Type:
Article
Affiliation country:
China