Journal
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
Volume 34, Issue 7, Pages 464-471Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/cbr.2018.2721
Keywords
antiangiogenic therapy; breast cancer; combined therapy; docetaxel; HUVEC vaccine
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Funding
- National Natural Science Foundation of China [81541158]
- Natural Science Foundation of Shandong Province [ZR2018QH005, ZR2018BH046]
- Project of Shandong Province Higher Educational Science and Technology Program [J15LM51, J15LE51]
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Background: A human umbilical vein endothelial cell (HUVEC) vaccine is a promising anti-angiogenesis therapy, but the modest therapeutic antitumor efficacy restricts its clinical use. Preclinical evidence supports the combination of antiangiogenic agents and chemotherapy for cancer treatment. Materials and Methods: In the present study, docetaxel (DOC) was combined with HUVEC vaccine to develop a HUVEC-DOC treatment regime. This study was designed to investigate the synergistic anti-breast cancer effects and mechanisms of the HUVEC-DOC treatment. Results: Compared with either agent monotherapy, HUVEC-DOC treatment exhibited more favorable anti-EMT-6 breast cancer effects in vivo. CD31 immunohistochemical analysis of the excised tumors showed notable decreases in vessel density after HUVEC-DOC administration, while T cells isolated from mice immunized with HUVEC-DOC showed increased cytotoxicity against HUVECs. Furthermore, the quantity of interferon gamma released from HUVEC-DOC-administered mice was significantly higher than the other three groups, and enhanced CD8(+) T cell infiltration was observed more frequently in tumors excised from HUVEC-DOC-treated mice. Finally, the percentage of regulatory T cells was significantly decreased after HUVEC-DOC immunization. Conclusions: All the data verified that combining DOC with a HUVEC vaccine could generate synergistic anti-breast cancer activity, which might have the potential for combination treatment of human breast cancer.
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