Anti-tumor Cytotoxicity of Allogeneic Neuroblastoma Tumor Antigen-loaded Dendiritic Cells

ABSTRACT

BACKGROUND: Despite of aggressive treatments, the long-term survival rate is about 30% in stage 4 neuroblastoma (NBL). Recently, dendritic cell (DC)-based immunotherapy is emerging as a promising tool in cancer treatment. But it is very difficult to get sufficient amount of autologous tumor as the source of tumor antigen in DC-based immunotherapy. The purpose of this study was to test whether DCs loaded with allogeneic NBL tumor antigens can prime effective anti-tumor immune responses. METHODS: Peripheral blood mononuclear cells (PBMCs) were differentiated into immature DCs in the presence of GM-CSF and IL-4. As the source of tumor antigens, human neuroblastoma cell lines, SK-N-MC, SK-N-SH, and IMR-32, were used after induction of apoptosis by UV irradiation. The immature DCs were loaded with apoptotic tumor cells, and then cultured with PBMCs for priming the tumor antigen-specific T lymphocytes. The tumor-specific cytotoxicity of T lymphocytes against NBL cells was analysed after coculture. RESULTS: Incubation of DCs with apoptotic tumor cells effectively loaded DCs with tumor antigens and induced maturation of DCs. The tumor antigen-challenged T lymphocytes effectively killed the NBL cells, which were used as tumor antigens. Furthermore, the T lymphocytes showed a broad ranged cytotoxicity to all of the NBL cell lines, which were not challenged as tumor antigens. CONCLUSION: This study showed that the apoptotic NBL tumor cells induced maturation of DCs and could be used as tumor antigens, and DCs loaded with apoptotic NBL tumor cells could induce effective anti-tumor specific cytotoxic T lymphocytes to allogeneic NBL tumors.