Dendritic cell-Ewing's sarcoma cell hybrids enhance antitumor immunity.
Given the effective immunotherapy of DC-based vaccine in other cancers, we hypothesized DC-based vaccines would induce effective immune responses against Ewing's sarcoma. To verify this hypothesis and develop the most effective dendritic cell vaccine against Ewing's sarcoma, we evaluated the antitumor efficacy of dendritic cell-Ewing's sarcoma hybrids and dendritic cells pulsed with other antigen-loading methods, including cell lysates and the characteristic EWS-FLI1 gene of Ewing's sarcoma, using an A673 cell line as a model. The hybrids were generated by electrofusion with fusion efficiency and viability determined by flow cytometry and fluorescent microscopy analyses. By interferon-gamma secretion assay, the capacity of hybrids to stimulate cytotoxic T-lymphocytes (CTLs) is higher than that of other antigen-loading methods showing stronger tumor antigen-specific CTL cytotoxicity to A673. By in vivo experiment in SCID mice, all dendritic cell-based strategies induced specific immune responses to Ewing's sarcoma after mice-human immune system reconstitution by inoculating human peripheral blood mononuclear cells into the peritoneal cavity of SCID mice. However, the hybrids most inhibited the subcutaneous tumor growth in SCID mice compared with dendritic cells pulsed with other loading methods. The data suggest A673 cells respond to dendritic cell-based immunotherapy.
Musculoskeletal Tumor Center, Peking University People's Hospital, #11 South Xizhimen Street, Beijing 100044, People's Republic of China. bonetumor@163.com
Wei
W
Guo
Yi
Y
Guo
Shun
S
Tang
Huayi
H
Qu
Hui
H
Zhao
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001859:Bone Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D015514:Oncogene Proteins, Fusion / Q000276:immunology; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012512:Sarcoma, Ewing / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; D007371:Interferon-gamma