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Updated: Oct 29, 2025
In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
Anti-tumor effects of vascular endothelial growth factor/vascular endothelial growth factor receptor binding
Haiyan Xing1, Xue Yang1, Yingxi Xu1
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
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.
Insights
Novel chimeric antigen receptor (CAR) T cells targeting vascular endothelial growth factor receptors (VEGFR-2/3) demonstrate potent anti-tumor activity against breast cancer. This approach enhances CAR T-cell therapy applications by inhibiting tumor growth, infiltration, and metastasis.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway is crucial for tumor angiogenesis and lymphangiogenesis.
- Inhibiting VEGF/VEGFR signaling is a key strategy in cancer therapy.
Purpose of the Study:
- To develop and evaluate a novel chimeric antigen receptor (CAR) T-cell therapy targeting both VEGFR-2 and VEGFR-3.
- To assess the anti-tumor efficacy of these engineered T cells against breast cancer.
Main Methods:
- Engineered T cells with a chimeric antigen receptor (CAR) lentiviral vector targeting VEGFR-2 and VEGFR-3 (VEGFR-2/3 CAR).
- Co-cultured VEGFR-2/3 CAR T cells with VEGFR-2/3-positive breast cancer cells.
- Evaluated cytotoxicity, cytokine secretion, and anti-tumor effects in vitro and in vivo using a mouse model.
Main Results:
- VEGFR-2/3 CAR T cells exhibited potent cytotoxicity against VEGFR-2 and VEGFR-3 positive breast cancer cells.
- Enhanced secretion of interferon gamma, tumor necrosis factor alpha, and interleukin-2 observed.
- Demonstrated inhibition of tumor growth, infiltration, and metastasis in an orthotopic mouse model.
Conclusions:
- VEGFR-2/3 CAR T cells possess significant anti-tumor activity.
- This novel CAR T-cell strategy expands therapeutic applications for cancer treatment.
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