Antitumor activity of patient-derived renal cell carcinoma cells fused with allogeneic dendritic cells: In vitro results and cli

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Background: Renal cell carcinoma (RCC) has been shown to be highly susceptible to immune-based treatment strategies.

 

Methods: In the present study, patient-derived tumor cells were fused with allogeneic dendritic cells (DC) to elicit antitumor activity against RCC. DC from HLA-A2+ healthy donors were fused with primary RCC cells from 10 patients. Phenotype of fusion cells was characterized by flow cytometer and confocal microscopy. In vitro, T-cell proliferation, IFN-? secretion, and cytotocic T lymphocytes (CTL) activity elicited by allogeneic DC/RCC fusion cells were assessed. Clinically, 10 patients were vaccinated with allogeneic DC/RCC fusion vaccine. The adverse effects and toxicity were observed. The clinical response was evaluated by CT scans.

 

Results: After fusion, the created hybrids expressed both tumor-associated antigen and DC-derived molecules and could stimulate the proliferation and IFN-? secretion of T-cells as well as elicit strong CTL activity against RCC cells in vitro. In vivo, neither serious adverse effects nor signs of autoimmune disease were observed after vaccination therapy. Percentage of T lymphocyte subsets in peripheral blood of patients was increased significantly. One of 10 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 year).

 

Conclusions: The data suggest that allogeneic DC/RCC fusion vaccine is safe and can elicit immunological responses in patients with RCC.