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Updated: May 14, 2026
Orthotopic Injection of Breast Cancer Cells into the Mice Mammary Fat Pad
Published on: January 20, 2019
Active immunotherapy for mouse breast cancer with irradiated whole-cell vaccine expressing VEGFR2
Heng-Xiu Yan1, Ping Cheng, Hai-Yan Wei
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, PR China.
Abstract:
As tumor-associated antigens are not well characterized for the majority of human tumors, polyvalent vaccines prepared with whole-tumor antigens are an attractive approach for tumor vaccination. Vascular endothelial growth factor receptor-2 (VEGFR2), as a model antigen with which to explore the feasibility of immunotherapy, has shown great promise as a tumor vaccine. However, the efficacy of immunotherapy is often not ideal when used alone. In this study, we explored the therapeutic efficacy of an irradiated AdVEGFR2-infected cell vaccine-based immunotherapy in the weakly immunogenic and highly metastatic 4T1 murine mammary cancer model. An adenovirus encoding the VEGFR2 gene (AdVEGFR2) was constructed. Lethally irradiated, virus-infected 4T1 cells were used as vaccines. Vaccination with lethally irradiated AdVEGFR2-infected 4T1 cells inhibited subsequent tumor growth and pulmonary metastasis compared with challenge inoculations. Angiogenesis was inhibited, and the number of CD8+ T lymphocytes was increased within the tumors. Antitumor activity was also caused by the adoptive transfer of isolated spleen lymphocytes. In vitro, the expression of HMGB1 and HSP70 in the AdVEGFR2‑infected 4T1 cells was increased, and was involved in the activation of tumor antigen-specific T-cell immunity. Our results indicate that the immunotherapy based on irradiated AdVEGFR2-infected whole-cancer cell vaccines may be a potentially effective strategy for 4T1 cancer treatment.
Insights
This study shows that an irradiated whole-cancer cell vaccine targeting vascular endothelial growth factor receptor-2 (VEGFR2) effectively inhibits 4T1 breast cancer growth and metastasis in mice, activating anti-tumor immunity.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Tumor-associated antigens are often unknown, making whole-tumor antigen vaccines attractive.
- Vascular endothelial growth factor receptor-2 (VEGFR2) is a promising target for cancer immunotherapy.
- Current immunotherapies often require combination strategies for optimal efficacy.
Purpose of the Study:
- To investigate the therapeutic efficacy of an irradiated adenovirus-vectored VEGFR2-infected cell vaccine in a 4T1 murine mammary cancer model.
- To explore the underlying mechanisms of anti-tumor immunity induced by this vaccine strategy.
Main Methods:
- Construction of an adenovirus encoding VEGFR2 (AdVEGFR2).
- Generation of vaccines using lethally irradiated, AdVEGFR2-infected 4T1 cells.
- Evaluation of tumor growth, metastasis, angiogenesis, and immune cell infiltration in vivo.
- Assessment of anti-tumor activity via adoptive transfer of spleen lymphocytes and in vitro analysis of HMGB1 and HSP70 expression.
Main Results:
- Vaccination with irradiated AdVEGFR2-infected 4T1 cells significantly inhibited tumor growth and pulmonary metastasis.
- The vaccine treatment led to reduced angiogenesis and increased CD8+ T lymphocyte infiltration in tumors.
- Adoptive transfer of spleen lymphocytes from vaccinated mice conferred anti-tumor activity.
- In vitro studies showed increased HMGB1 and HSP70 expression in infected cells, contributing to T-cell activation.
Conclusions:
- Irradiated AdVEGFR2-infected whole-cancer cell vaccines represent a potentially effective immunotherapy strategy for 4T1 breast cancer.
- This approach harnesses tumor antigen-specific T-cell immunity, potentially through elevated HMGB1 and HSP70.
- The findings support further investigation of whole-cancer cell vaccines for treating metastatic cancers.
