Cancer vaccine therapy using dendritic cells (DCs) adenovirally transduced with the tumor antigen gene: Comparative analysis to DCs pulsed with the immunodominant peptide Free

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Dendritic cells (DCs) are potent antigen-presenting cells and could be an attractive candidate for cancer immunotherapy. Recently, several studies have shown that vaccine therapy using DCs genetically engineered to express a surrogate tumor antigen. In this study, we examined therapeutic efficacy of the immunotherapy using DCs genetically engineered to express the tumor antigen, comparing to the immunotherapy using DCs pulsed with the tumor antigen peptide. Bone marrow-derived murine DCs were adenovirally transduced with natural tumor antigen gp70 gene of BALB/c-derived CT26 (DC-Axgp70). On the other hand, DCs were pulsed with AH-1 which is immunodominant peptide of the gp70 (DC/AH-1). The cytotoxic T lymphocyte (CTL) activity against CT26 induced in the mice immunized with DCs-Axgp70 showed significantly higher (40%) than that in the mice immunized with DC/AH-1 (24%)(E/T:50, p<0.0005). In the subcutaneous tumor model and the orthotopic colon cancer model of CT26, the vaccine therapy using DC-Axgp70 showed much more remarkable inhibition of tumor growth than the vaccination using DC/AH-1 (p<0.0001), which was reflected in resulting in the prolongation of the survival periods. CC chemokine receptor 7 mRNA expression on DCs, which would play an important role in the migration of DCs to regional lymph nodes was induced by adenoviral transduction with gp70 gene. In contrast, it was not detected in AH-1-pulsed DCs. These results suggested that the vaccination using DCs transduced with the tumor antigen gene could be a more potent strategy for therapeutic antitumor immunotherapy than the vaccination with the immunodominant peptide-pulsed DCs.