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Patient-derived renal cell carcinoma cells fused with allogeneic dendritic cells elicit anti-tumor activity: in vitro results and clinical responses

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Abstract

Renal cell carcinoma (RCC) has been shown to be susceptible to immunotherapeutic treatment strategies. In the present study, patient-derived tumor cells were fused with allogeneic dendritic cells (DC) to elicit anti-tumor activity against RCC. DC from HLA-A2+ healthy donors were fused with primary RCC cells from ten patients. Phenotype of fusion cells were characterized by flow cytometer and confocal microscopy. In vitro, T cell proliferation, IFN-γ secretion and cytotocic T lymphocytes (CTL) activity elicited by allogeneic DC/RCC fusion cells were assessed. Clinically, ten patients were vaccinated with allogeneic DC/RCC fusion vaccine. The adverse effects and toxicity were observed. The clinical response was evaluated by CT scans. After fusion, the created hybrids expressed both tumor associated antigen and DC-derived molecules and could stimulate the proliferation and IFN-γ secretion of T cells as well as elicit strong CTL activity against RCC cells in vitro. In vivo, no serious adverse effects, toxicity, or signs of autoimmune disease were observed after vaccination therapy. Percentage of T lymphocyte subsets in peripheral blood of patients was increased significantly. One of ten patients exhibited a partial response with regression of lung metastases. Six patients showed stable disease with stabilization of previously progressive disease (follow up 1.5 years). The PR and SD responses, exhibited by 7/10 patients who received the allogeneic DC/RCC fusion vaccine treatment, suggest that this approach is safe and can elicit immunological responses in a significant portion of patients with RCC.

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Acknowledgments

This work was supported by the Science and Technology Planning Project of Guangdong Province (2004B30301017).

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Authors and Affiliations

  1. State Key Laboratory of Oncology in Southern China, 510060, Guangzhou, People’s Republic of China

    Jun Zhou, Desheng Weng, Ke Pan, Haifeng Song, Qijing Wang, Hui Wang, Yongqiang Li, Lixi Huang, Huakun Zhang, Wei Huang & Jianchuan Xia

  2. Biotherapy Center, Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, 510060, Guangzhou, People’s Republic of China

    Jun Zhou, Desheng Weng, Ke Pan, Haifeng Song, Qijing Wang, Huan Wang, Yongqiang Li, Lixi Huang, Huakun Zhang, Wei Huang & Jianchuan Xia

  3. Department of Urology, Cancer Center, Sun Yat-sen University, Guangzhou, People’s Republic of China

    Fangjian Zhou & Hui Wang

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  1. Jun Zhou
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  2. Desheng Weng
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  3. Fangjian Zhou
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  10. Lixi Huang
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  11. Huakun Zhang
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  12. Wei Huang
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  13. Jianchuan Xia
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Correspondence to Jianchuan Xia.

Additional information

J. Zhou and D. Weng contributed equally.

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Zhou, J., Weng, D., Zhou, F. et al. Patient-derived renal cell carcinoma cells fused with allogeneic dendritic cells elicit anti-tumor activity: in vitro results and clinical responses. Cancer Immunol Immunother 58, 1587–1597 (2009). https://doi.org/10.1007/s00262-009-0668-9

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  • DOI: https://doi.org/10.1007/s00262-009-0668-9

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