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Dendritic Cells stimulated with outer membrane protein A (OmpA) of Salmonella typhimurium generate effective anti-tumor immunity

Authors
Jang, Min JaKim, Jee-EunChung, Yoon HeeLee, Won BokShin, Yong KyooLee, Jun SikKim, DaejinPark, Yeong-Min
Issue Date
16-Mar-2011
Publisher
ELSEVIER SCI LTD
Keywords
Dendritic cells; Outer membrane protein A; Anti-tumor immunity
Citation
VACCINE, v.29, no.13, pp 2400 - 2410
Pages
11
Journal Title
VACCINE
Volume
29
Number
13
Start Page
2400
End Page
2410
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/12620
DOI
10.1016/j.vaccine.2011.01.036
ISSN
0264-410X
1358-8745
Abstract
Gram-negative bacterial outer membrane proteins (Omps) have an important role in pathogenesis and signal reception. We previously reported that Acinetobacter OmpA (AbOmpA) induced maturation of bone marrow-derived dendritic cells (BMDCs) and that AbOmpA-primed DCs produced IL-12 which generated Th1 CD4(+) T-cells. We analyzed the effects of Salmonella typhimurium OmpA (OmpA-Sal) on dendritic cell (DC) maturation in the present study, and determined that tumor antigen-pulsed DCs stimulated with OmpA-Sal induced anti-tumor responses in a mouse model. OmpA-Sal activated BMDCs by augmenting expression of MHC class II and of the co-stimulatory molecules CD80 and CD86. RT-PCR revealed that IL-12(p40) gene expression is highly augmented in OmpA-Sal-stimulated BMDCs. DNA (CRT/E7) vaccination combined with OmpA-Sal stimulation generated more antigen-specific CD8(+) T-cells in the present study. Certain antigen-pulsed BMDCs stimulated with OmpA-Sal induced strong PADRE-specific CD4(+) and E7-specific CDS+ T-cell responses. In addition, BMDCs stimulated with OmpA-Sal (OmpA-Sal-BMDCs) and pulsed with both E7 and PADRE peptide generated greater numbers of E7-specific CDS+ effector and memory T-cells than those pulsed with E7 peptide alone. E7- and PADRE-expressing OmpA-Sal-BMDC vaccines resulted in significant long-term protective anti-tumor effects in vaccinated mice. Our data suggested that E7- and PADRE-expressing BMDCs that were matured in the presence of OmpA-Sal might enhance anti-tumor immunity and support the therapeutic use of OmpA-Sal in DC-based immunotherapy. (C) 2011 Elsevier Ltd. All rights reserved.
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