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Improved efficacy of therapeutic vaccination with viable human umbilical vein endothelial cells against murine melanoma by introduction of OK432 as adjuvant

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Tumor Biology

Abstract

Vaccination with xenogeneic or syngeneic endothelial cells targeting tumor angiogenesis is effective for inhibiting tumor growth. OK432, an effective adjuvant, was mixed with viable human umbilical vein endothelial cells (HUVECs) to prepare a novel HUVECs-OK432 vaccine, which could have an improved therapeutic efficacy. In this study, HUVECs-OK432 was administrated in mice by subcutaneous injection in a therapeutic procedure. The results showed that a stronger HUVEC-specific Abs and cytotoxic T lymphocyte immune response were elicited, which resulted in significant inhibition on the growth of B16F10 melanoma and remarkably prolonged survival of B16F10 melanoma-bearing mice compared with HUVECs. Besides, parallel results were obtained in vitro showing a stronger inhibition of HUVEC proliferation by immune sera of HUVECs-OK432 than that of HUVECs. Moreover, histochemistry and immunohistochemistry analysis showed that HUVECs-OK432 induced large areas of continuous necrosis within tumors and significantly reduced the vessel density, correlating well with the extent of tumor inhibition. Our present results suggest that OK432 could be employed as an effective adjuvant for HUVEC vaccines and therefore should be useful for adjuvant immunotherapy of cancer.

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Acknowledgments

The authors thank Lifeng Jiang (Department of State Key Laboratory of Natural Medicine, China Pharmaceutical University, People's Republic of China) for critical reading of the manuscript. The authors thank group members for assistance with animal experiments, especially Zeyu Wang, Xiuhua Zhang, Lei Lu, Bin Liu, Xiao Huang, Yuankai Dong, Jianfeng Zhuang, Fei Li, Meng Chen, Xiaorui Liu, and Mengmeng Han.

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Authors and Affiliations

  1. Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People’s Republic of China

    Maolei Xu, Yun Xing, Xue Yang, Wenjun Yao, Wen Xiao, Chiyu Ge, Yanjun Ma, Jie Yang, Jie Wu, Rongyue Cao, Taiming Li & Jingjing Liu

  2. State Key Laboratory of Natural Medicine, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People’s Republic of China

    Ling Zhou

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  1. Maolei Xu
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Correspondence to Taiming Li or Jingjing Liu.

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Maolei Xu and Yun Xing contributed equally to this paper.

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Xu, M., Xing, Y., Zhou, L. et al. Improved efficacy of therapeutic vaccination with viable human umbilical vein endothelial cells against murine melanoma by introduction of OK432 as adjuvant. Tumor Biol. 34, 1399–1408 (2013). https://doi.org/10.1007/s13277-012-0616-8

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  • DOI: https://doi.org/10.1007/s13277-012-0616-8

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