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Low-dose paclitaxel enhances the anti-tumor efficacy of GM-CSF surface-modified whole-tumor-cell vaccine in mouse model of prostate cancer

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Abstract

Chemotherapy combined with a tumor vaccine is an attractive approach in cancer therapy. This study was designed to investigate the optimal schedule and mechanisms of action of a novel GM-CSF (granulocyte–macrophage colony-stimulating factor) surface-modified tumor-cell vaccine in combination with paclitaxel in the treatment of mouse RM-1 prostate cancer. First, the anti-tumor efficiencies of various dosage of paclitaxel (4, 20, 40 mg/kg) in combination with the vaccine in different administration sequences were examined in the mouse RM-1 prostate cancer model. Then, the in vivo and in vitro effects of various dosage of paclitaxel on RM-1 cells, T cells, and DCs (dendritic cells) were evaluated. The results showed that: (a) the GM-CSF-surface-modified tumor-cell vaccine was more potent at inducing the uptake of tumor antigens by DCs than irradiated tumor cells plus free GM-CSF; (b) 4 mg/kg paclitaxel combined with the GM-CSF-surface-modified tumor-cell vaccine was the most effective at enhancing tumor regression in RM-1 prostate cancer mice when the vaccine was administrated 2 days after paclitaxel; and (c) administration of 4 mg/kg paclitaxel followed by the vaccine induced the highest degree of CD8+ T-cell infiltration in tumor tissue, suggesting that the induction of tumor-specific immune response had occurred. These findings suggested that the GM-CSF-surface-modified tumor-cell vaccine may have potential clinical benefit for patients with prostate cancer when it is combined with paclitaxel. Furthermore, the effect of immunochemotherapy depends on careful selection of paclitaxel dosage and the sequence of paclitaxel/vaccine administration.

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Acknowledgments

This work was supported in part by grants from Chinese National 863 plan (2006AA02Z4C4), the Natural Science Foundation of China (30928023 and 30971516), Zhejiang Provincial Major Research Program (2007C13020 and 2008C14082), the Natural Science Foundation of Zhejiang Province (R2080407 and Y2100925), Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents, Science & Technology Innovation Program for College/University Students in Zhejiang Province (2009R413042 and 2010R413047) and Wenzhou Municipal Research Program (G20090142).

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Authors and Affiliations

  1. Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, University Park, 325035, Wenzhou, China

    Qiushan He, Zhichun Song, Jia Tang, Demin Wu, Yue Lu, Zhen Wang, Dan Liu, Xiaoren Zhang & Jimin Gao

  2. Institute of Biotherapy, School of Biotechnology, Southern Medical University, Guangzhou, China

    Jinlong Li, Weihua Yin, Zhen Zhang & Zhiming Hu

  3. Department of Oncology, Affiliated Xiangfan Hospital, Tongji Medical College, Huazhong Scientific and Technical University, Xiangfan, China

    Qiushan He & Tienan Yi

  4. 1838 Guangzhou da dao bei, Guangzhou, 510515, China

    Zhiming Hu

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  1. Qiushan He
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  2. Jinlong Li
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  3. Weihua Yin
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Correspondence to Zhiming Hu or Jimin Gao.

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Q. He and J. Li contributed equally to this study.

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He, Q., Li, J., Yin, W. et al. Low-dose paclitaxel enhances the anti-tumor efficacy of GM-CSF surface-modified whole-tumor-cell vaccine in mouse model of prostate cancer. Cancer Immunol Immunother 60, 715–730 (2011). https://doi.org/10.1007/s00262-011-0988-4

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  • DOI: https://doi.org/10.1007/s00262-011-0988-4

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