Korean J Hematol 2007; 42(2):
Published online June 30, 2007
https://doi.org/10.5045/kjh.2007.42.2.136
© The Korean Society of Hematology
박현진, 신희영, 안효섭
국립암센터 특수암센터 소아종양클리닉, 서울대학교 의과대학 소아과학교실, 암연구소
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.
Keywords Dendritic cell, Immunotherapy, Allogeneic tumor antigen, Neuroblastoma
Korean J Hematol 2007; 42(2): 136-145
Published online June 30, 2007 https://doi.org/10.5045/kjh.2007.42.2.136
Copyright © The Korean Society of Hematology.
박현진, 신희영, 안효섭
국립암센터 특수암센터 소아종양클리닉, 서울대학교 의과대학 소아과학교실, 암연구소
Hyeon Jin Park, Hee Young Shin, Hyo Seop Ahn
Pediatric Oncology Branch, Specific Organs Cancer Center, National Cancer Center
Department of Pediatrics, Cancer Research Institute
Seoul National University College of Medicine, Seoul, Korea
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.
Keywords: Dendritic cell, Immunotherapy, Allogeneic tumor antigen, Neuroblastoma
Yoon Seok Choi
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