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-γ-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.
Highlights
Cancer immunotherapy based on dendritic cell (DC) vaccination is an exciting prospect for the treatment of cancer (Banchereau and Palucka, 2005)
It has been reported that 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 cancer patients with gastrointestinal cancer (ValladaresAyerbes et al, 2008)
Several studies have revealed that tumor-associated antigen (TAA) gene-modified DCs can provide extended antigen presentation and induce antigen-specific cytotoxic T lymphocyte (CTL) more efficiently than peptide pulsing (Nakamura et al, 2005)
Summary
Cancer immunotherapy based on dendritic cell (DC) vaccination is an exciting prospect for the treatment of cancer (Banchereau and Palucka, 2005). A central tenet of cancer immunotherapy is the generation of an antigen-specific cytotoxic T lymphocyte (CTL) response (Melief et al, 2002). The CTL response is dependent on suitable tumorassociated antigens (TAAs). TAAs can induce T lymphocytes that recognize tumors, but not normal tissues (Parmiani et al, 2007). TAAs should be expressed in a significant proportion of tumor cells and are obligatory for the survival of tumor cells. DCs pulsed with various TAAs have been shown to be effective in producing specific anti-tumor effects in vitro and in vivo (Nakamura et al, 2005)
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