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.
10.3858/emm.2012.44.1.006
- Author:
Hyun Ju LEE
1
;
Cheol Yi HONG
;
Mi Hyun KIM
;
Youn Kyung LEE
;
Thanh Nhan NGUYEN-PHAM
;
Byoung Chul PARK
;
Deok Hwan YANG
;
Ik Joo CHUNG
;
Hyeoung Joon KIM
;
Je Jung LEE
Author Information
1. Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun 519-763, Korea. drjejung@chonnam.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
AGR2 protein, human;
antigens, neoplasm;
colorectal neoplasms;
dendritic cells;
immunotherapy, active
- MeSH:
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
- From:Experimental & Molecular Medicine
2012;44(1):60-67
- CountryRepublic of Korea
- Language:English
-
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.
