Exp Mol Med.
2012 Jan;44(1):60-67. 10.3858/emm.2012.44.1.006.
In vitro induction of anterior gradient-2-specific cytotoxic T lymphocytes by dendritic cells transduced with recombinant adenoviruses as a potential therapy for colorectal cancer
- Affiliations
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- 1Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun 519-763, Korea. drjejung@chonnam.ac.kr
- 2Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun 519-763, Korea.
- 3Vaxcell-Bio Therapeutics, Hwasun 519-763, Korea.
- 4Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Korea.
- 5The Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju 500-757, Korea.
- KMID: 1120143
- DOI: http://doi.org/10.3858/emm.2012.44.1.006
Abstract
- Anterior gradient-2 (AGR2) promotes tumor growth, cell migration, and cellular transformation, and is one of the specific mRNA markers for circulating tumor cells in patients with gastrointestinal cancer. We investigated the feasibility of AGR2 as a potent antigen for tumor immunotherapy against colorectal cancer (CRC) cells using dendritic cells (DCs) transduced with a recombinant adenovirus harboring the AGR2 gene (AdAGR2). DCs transduced with a recombinant adenovirus encoding the AGR2 gene (AdAGR2/DCs) were characterized. These genetically-modified DCs expressed AGR2 mRNA as well as AGR2 protein at a multiplicity of infection of 1,000 without any significant alterations in DC viability and cytokine secretion (IL-10 and IL-12p70) compared with unmodified DCs as a control. In addition, AdAGR2 transduction did not impair DC maturation, but enhanced expression of HLA-DR, CD80, and CD86. AdAGR2/DCs augmented the number of IFN-gamma-secreting T-cells and elicited potent AGR2-specific cytotoxic T lymphocytes capable of lysing AGR2-expressing CRC cell lines. These results suggest that AGR2 act as a potentially important antigen for immunotherapy against CRC in clinical applications.
Keyword
MeSH Terms
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Adenoviridae
Antigen Presentation/genetics
Antigens, Neoplasm/immunology
Carcinoma/*therapy
Cell Line, Tumor
Colorectal Neoplasms/*therapy
Cytotoxicity, Immunologic/genetics
Dendritic Cells/immunology
Humans
*Immunotherapy, Adoptive
Interferon-gamma/secretion
Lymphocyte Activation/genetics
Proteins/genetics/*metabolism
T-Lymphocytes, Cytotoxic/*immunology
Transduction, Genetic
Transgenes/genetics
Tumor Markers, Biological/immunology
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