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

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 CD8(+) 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 CD8(+) 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.

• Authors: Min Ja Jang, Jee-Eun Kim, Yoon Hee Chung, Won Bok Lee, Yong Kyoo Shin, Jun Sik Lee, Daejin Kim, Yeong-Min Park
• Journal: Vaccine (Vaccine) Vol. 29 Issue 13 Pg. 2400-10 (Mar 16 2011) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 21276440 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Antigens, Surface
• Bacterial Outer Membrane Proteins
• Cancer Vaccines
• Cytokines
• OMPA outer membrane proteins

Topics

• Animals
• Antigens, Neoplasm (immunology)
• Antigens, Surface (analysis)
• Bacterial Outer Membrane Proteins (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology)
• Cytokines (biosynthesis)
• Dendritic Cells (chemistry, immunology)
• Female
• Gene Expression Profiling
• Mice
• Mice, Inbred C57BL
• Neoplasms (prevention & control)
• Reverse Transcriptase Polymerase Chain Reaction
• Salmonella typhimurium (immunology)