Original Article

Cancer Immunology, Immunotherapy

, 58:1587

First online:

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

  • Jun ZhouAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
  • , Desheng WengAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
  • , Fangjian ZhouAffiliated withDepartment of Urology, Cancer Center, Sun Yat-sen University
  • , Ke PanAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
  • , Haifeng SongAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
  • , Qijing WangAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
  • , Huan WangAffiliated withBiotherapy Center, Cancer Center, Sun Yat-sen University
  • , Hui WangAffiliated withState Key Laboratory of Oncology in Southern ChinaDepartment of Urology, Cancer Center, Sun Yat-sen University
  • , Yongqiang LiAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
    • , Lixi HuangAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
    • , Huakun ZhangAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
    • , Wei HuangAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University
    • , Jianchuan XiaAffiliated withState Key Laboratory of Oncology in Southern ChinaBiotherapy Center, Cancer Center, Sun Yat-sen University Email author 

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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.

Keywords

Dendritic cell Renal cell carcinoma Cell fusion T cell activation Immunotherapy