Tumor cells with B7.1 and transmembrane anchored staphylococcal enterotoxin A generate effective antitumor immunity

Staphylococcus enterotoxin A (SEA) stimulates T cells bearing certain TCR β-chain variable regions, when bound to MHC-II molecules, and is a potent inducer of CTL activity and cytokines production. To decrease toxicity of SEA to the normal MHC-II + cells and to localize the immune response induced b...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-08, Vol.347 (1), p.208-214
Main Authors: Si, Shao-Yan, Hu, Pei-Zhen, Huang, Ya-Yu, Ye, Jing, Huang, Yang, Li, Zeng-Shan, Ge, Wei, Li, Xia, Qu, Ping, Zhang, Xiu-Min, Sui, Yan-Fang
Format: Article
Language:English
Subjects:
Animals
B7-1 Antigen - genetics
B7-1 Antigen - immunology
Cancer Vaccines - administration & dosage
Cancer Vaccines - immunology
Cell Line, Tumor
Disease Models, Animal
Enterotoxins - genetics
Enterotoxins - immunology
Female
Immunity, Innate - immunology
Immunotherapy
Melanoma - immunology
Melanoma - pathology
Melanoma - prevention & control
Mice
Mice, Inbred C57BL
Murine B7.1
Staphylococcus
Staphylococcus enterotoxin A
Treatment Outcome
Tumor vaccine
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Summary:Staphylococcus enterotoxin A (SEA) stimulates T cells bearing certain TCR β-chain variable regions, when bound to MHC-II molecules, and is a potent inducer of CTL activity and cytokines production. To decrease toxicity of SEA to the normal MHC-II + cells and to localize the immune response induced by SEA to the tumor site, my colleague previously genetically fused SEA with B7.1 transmembrane region (named as SEAtm) to make SEA express on the surface of tumor cells and tumor cells modified with SEAtm could induce efficient antitumor immunity in vitro. The tumor cell vaccines modified with multiple immune activators frequently elicited stronger antitumor immune responses than single-modified vaccines. In this study, we modified the tumor cell vaccine with B7.1 and SEAtm to improve efficiency in the application of SEA. First, SEAtm gene was subcloned from recombinant plasmid pLXSNSEP by PCR and murine B7.1 gene was cloned from splenocytes derived from C57BL/6 mice by RT-PCR. Then, the eukaryotic co-expression vector of SEA and murine B7.1 gene was constructed and named as pcDNA-BIS. B16 cell lines stably expressing SEA and/or B7.1 were established by screening with G418 after transfection and inactivated for the preparation of tumor cell vaccines to treat mice bearing established B16 tumors. The results indicated that the dual-modified tumor cell vaccine B16/B7.1 + SEAtm (B16-BIS) elicited significantly stronger antitumor immune responses in vivo when compared with the single-modified tumor cell vaccines B16/B7.1 (B16-B7.1) and B16/SEAtm (B16-SEAtm), and supported the feasibility and effectiveness of the dual-modified tumor cell vaccine with superantigen and co-stimulatory molecule.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2006.06.080