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Improved Antitumor Efficacy of Combined Vaccine Based on the Induced HUVECs and DC-CT26 Against Colorectal Carcinoma

1
Department of Pathophysiology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, Henan, China
2
Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou 450001, Henan, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Cells 2019, 8(5), 494; https://doi.org/10.3390/cells8050494
Received: 24 April 2019 / Revised: 20 May 2019 / Accepted: 21 May 2019 / Published: 22 May 2019
(This article belongs to the Special Issue Angiogenesis in Cancer)
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Abstract

Angiogenesis is essential for the development, growth, and metastasis of solid tumors. Vaccination with viable human umbilical vein endothelial cells (HUVECs) has been used for antitumor angiogenesis. However, the limited immune response induced by HUVECs hinders their clinical application. In the present study, we found that HUVECs induced by a tumor microenvironment using the supernatant of murine CT26 colorectal cancer cells exerted a better antiangiogenic effect than HUVECs themselves. The inhibitory effect on tumor growth in the induced HUVEC group was significantly better than that of the HUVEC group, and the induced HUVEC group showed a strong inhibition in CD31-positive microvessel density in the tumor tissues. Moreover, the level of anti-induced HUVEC membrane protein antibody in mouse serum was profoundly higher in the induced HUVEC group than in the HUVEC group. Based on this, the antitumor effect of a vaccine with a combination of induced HUVECs and dendritic cell-loading CT26 antigen (DC-CT26) was evaluated. Notably, the microvessel density of tumor specimens was significantly lower in the combined vaccine group than in the control groups. Furthermore, the spleen index, the killing effect of cytotoxic T lymphocytes (CTLs), and the concentration of interferon-γ in the serum were enhanced in the combined vaccine group. Based on these results, the combined vaccine targeting both tumor angiogenesis and tumor cells may be an attractive and effective cancer immunotherapy strategy. View Full-Text
Keywords: angiogenesis; human umbilical vein endothelial cell; vaccine; tumor microenvironment; dendritic cell; colorectal carcinoma angiogenesis; human umbilical vein endothelial cell; vaccine; tumor microenvironment; dendritic cell; colorectal carcinoma
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zhang, Q.; Xie, C.; Wang, D.; Yang, Y.; Liu, H.; Liu, K.; Zhao, J.; Chen, X.; Zhang, X.; Yang, W.; Li, X.; Tian, F.; Dong, Z.; Lu, J. Improved Antitumor Efficacy of Combined Vaccine Based on the Induced HUVECs and DC-CT26 Against Colorectal Carcinoma. Cells 2019, 8, 494.

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