Efficiency of colon cancer RNA-transfected DC vaccine is enhanced by previous treatment of tumor cells with low concentration of 5-fluorouracil (162.11)

Abstract

Abstract We have recently observed that human DCs treated with low doses of antitumor chemotherapeutic agents became them more efficient to stimulate T lymphocytes, whereas treatment of tumor cells with low concentrations of drugs made them more immunogenic than wild type cells. In this study we aimed to evaluate whether transfection of DC with drug-treated tumor cells RNA, enhances the effectiveness of DC-based vaccine, and if modulatory effects of drugs can be observed in vivo. To achieve these goals, C57/Bl-6 mice were s.c inoculated with MC-38 cells and 10 days later they were treated with DC transfected with RNA from MC-38 cells pre-treated with the minimum effective concentration of 5-fluorouracil (5-FU). Vaccination with these DC decreased the tumor growth, being the tumor size 40% lower than the Control. DC phenotyping showed that transfection increased the percentage of CD86+ (55% higher than control), CD40+ (57% higher), and MHC class II+ cells (58% higher). Spleen cells of tumor-bearing mice were co-cultured with MC-38 target cells and the supernatants evaluated for IFN-γ. Vaccination with transfected-DC was able to increase the in vitro production of IFN, compared with control. Our results suggest that treatment of tumor cells with minimum effective concentration of 5-FU induces transcriptional changes that can be transfered to DC by RNA transfection, enhancing their ability to stimulate the antitumor response.