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A bystander cell-based GM-CSF secreting vaccine synergized with a low dose of cyclophosphamide presents therapeutic immune responses against murine hepatocellular carcinoma

Cellular & Molecular Immunology volume 10, pages 349–359 (2013)Cite this article

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting cellular tumor vaccines contribute to the induction of potent antitumor immune responses in murine models and patients suffering from cancers. Hepatocellular carcinoma (HCC) is one of the most frequent and malignant cancers in China. We describe, for the first time, a GM-CSF releasing vaccine strategy that represents a step toward combating this type of cancer. In this study, a bystander cell-based GM-CSF secreting vaccine against murine HCC, Hepa1–6/B78H1-GM-CSF, was co-administered with a low dose of cyclophosphamide (CY). After challenging with tumor and vaccination, immunological assays demonstrated that the cellular antitumor immune responses were efficiently activated and that tumor development was significantly retarded, which was dependent on synergy with CY. The promising outcome of the anti-HCC vaccine in the murine model demonstrates the feasibility of a future clinical application for this treatment in HCC patients.

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Acknowledgements

This work was supported by grants from National Basic Research Program of China (2012CB910800 to BS), the National Natural Science Foundation (81072029 to BS and 30901750, 81272322 to YC, 81201528 to RJ), Major Research Plan of the National Natural Science Foundation (91029721 to BS), Natural Science Foundation of Jiangsu Province (BK2010532 to YC), China Postdoctoral Science Foundation-funded project (20090461133 to YC), Jiangsu Planned Projects for Postdoctoral Research Funds (1001028B to YC), Jiangsu Province Laboratory of Pathogen Biology (11BYKF02 to QS), Ministry of Health Research Foundation, China (LW201001 to LD) and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The work was also supported in part by the Program for Development of Innovative Research Teams in the First Affiliated Hospital of NJMU.

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Author notes

  1. Chen Chen and Jiajie Hou: Chen Chen and Jiajie Hou equally contribute to this work.

  2. Dr Y Chen, Department of Microbiology and Immunology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, China. E-mail: chenyun@njmu.edu.cn

  3. Dr B Sun, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China. E-mail: sunbc@njmu.edu.cn

Authors and Affiliations

  1. Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Chen Chen, Jiajie Hou, Zhe Lin, Ming Yao, Runqiu Jiang, Youjing Wang, Yun Gao, Lei Deng, Yun Chen & Beicheng Sun

  2. Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China

    Zhe Lin & Yun Chen

  3. Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Qing Shao

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  1. Chen Chen
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Chen, C., Hou, J., Lin, Z. et al. A bystander cell-based GM-CSF secreting vaccine synergized with a low dose of cyclophosphamide presents therapeutic immune responses against murine hepatocellular carcinoma. Cell Mol Immunol 10, 349–359 (2013). https://doi.org/10.1038/cmi.2013.20

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