期刊
VACCINE
卷 37, 期 15, 页码 2090-2098出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2019.02.055
关键词
Breast cancer; Immunization; VEGF; T regulatory cell; Tumor vaccine; Mucin 1
资金
- Henan Province Science and Technology Key Project [182102310337]
- Major Science and Technology Projects of Henan Province [161100310900]
Compelling evidence has shown that blocking VEGF via monoclonal antibodies may be beneficial in that it not only inhibits tumor angiogenesis but also reduces immune suppression and promotes T cell infiltration into tumors. Herein, we determined whether our recently generated VEGF165b mutant could be used as a co-immunization adjunct to augment the peptide cancer-vaccine-induced immune response in a mouse model of breast cancer. When co-immunized mVEGF165b with the peptide-based cancer vaccine (MUC1, a T-cell epitope dominant peptide vaccine from Mucin1), the VEGF antibody titers increased approximately 600,000-fold in mice. Moreover, the anti-VEGF antibody also reduced the frequency of regulatory T cells (Tregs) in both preventive and therapeutic scenarios. Mechanistically, the decrease of the Tregs population was associated with a remarkably increased MUC-1-specific IFN-gamma-producing CD8(+) T cells and anti-MUC1 humoral response. Finally, this combination co-immunization produced a superior antitumor response and significantly prolonged survival of tumor-bearing mice. In conclusion, our findings suggest that mVEGF165b may be an ideal immunization adjunct to enhance the immune efficacy of peptide-based tumor vaccines by overcoming immune tolerance. (C) 2019 Elsevier Ltd. All rights reserved.
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