Article

Dendritic cell-Ewing's sarcoma cell hybrids enhance antitumor immunity.

Musculoskeletal Tumor Center, Peking University People's Hospital, #11 South Xizhimen Street, Beijing 100044, People's Republic of China.
Clinical Orthopaedics and Related Research (impact factor: 2.53). 07/2008; 466(9):2176-83. DOI:10.1007/s11999-008-0348-7 pp.2176-83
Source: PubMed

ABSTRACT 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.

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Keywords

A673 cell line
 
antigen-loading methods
 
cell lysates
 
characteristic EWS-FLI1 gene
 
dendritic cell-based immunotherapy
 
dendritic cell-based strategies induced specific immune responses
 
dendritic cell-Ewing's sarcoma hybrids
 
dendritic cells pulsed
 
effective dendritic cell vaccine
 
Ewing's sarcoma
 
fluorescent microscopy analyses
 
fusion efficiency
 
inoculating human peripheral blood mononuclear cells
 
interferon-gamma secretion assay
 
mice-human immune system reconstitution
 
SCID mice
 
stimulate cytotoxic T-lymphocytes
 
stronger tumor antigen-specific CTL cytotoxicity
 
verify
 
vivo experiment
 

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