Enhanced anti-tumor immunity against breast cancer induced by whole tumor cell vaccines genetically modified expressing α-Gal epitopes

Xue,Dabing; Liang,Ying; Duan,Siliang; He,Jian; Su,Jing; Zhu,Jianmeng; Hu,Nan; Liu,Jianming; Zhao,Yongxiang; Lu,Xiaoling

doi:10.3892/or.2016.5128

Enhanced anti-tumor immunity against breast cancer induced by whole tumor cell vaccines genetically modified expressing α-Gal epitopes

Authors:
- Dabing Xue
- Ying Liang
- Siliang Duan
- Jian He
- Jing Su
- Jianmeng Zhu
- Nan Hu
- Jianming Liu
- Yongxiang Zhao
- Xiaoling Lu
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Affiliations: National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Respiratoy Diseases, The Third Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: September 23, 2016 https://doi.org/10.3892/or.2016.5128
Pages: 2843-2851

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Abstract

Whole tumor cell vaccines have shown much promise, but demonstrated poor efficiency in phase III trials. In this study, we modified MDA-MB‑231 tumor cells (MDA-MB‑231Gal+) to express α-1, 3-galactosyltransferase (α-1, 3-GT) protein, to potentially enhance antitumor effect of whole tumor cell vaccines. MDA-MB‑231 tumor cell vaccines were transfected with a reconstructed lentiviral containing α-1, 3-GT genes. Tumor growth, tumorigenesis and survival of Hu-NOD-SCID mice were observed when tumor-bearing mice were injected with tumor cell vaccines. Proliferation and apoptosis in MDA-MB‑231 tumor xenografts were observed by immunohistochemistry. The levels of cytokine secretion in the serum of mice were tested by ELISA. CD8+ T cells infiltrating tumors were assessed by flow cytometry. MDA-MB‑231Gal+ cells expressed active α-1, 3-GT and produced α-Gal in vitro. MDA-MB‑231Gal+ cell vaccines suppressed tumor growth and tumorigenesis in immunized Hu-NOD-SCID mice. Additionally, decrease of TGF-β, IL-10 and increase of INF-γ, IL-12 were observed in tumor cell vaccinated mice. Furthermore, the cell vaccines enhanced infiltration of cytotoxic CD8+ T cells in the tumor microenvironment of immunized mice. The MDA-MB‑231Gal+ cell vaccines modified α-1, 3-GT genes improved the antitumor effect.

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