Immunity against murine melanomas elicited by dendritic cells infected with adenovirus encoding human tyrosine-related protein 2

Objective: To compare the difference in immunity against murine melanomas elicited by dendritic cells infected with adenovirus encoding human or murine tyrosinase-related protein 2 (Ad hTRP2 or Ad mTRPZ). Methods: Analysis of the killing activity and production of IFN-γ by antigen-specific cytotoxic T lymphocytes(CTL) from the C57BL/6 mice immunized subcutaneously with bone marrow-derived dendritic cells (BM-DC) infected with adenovirus encoding human or murine TRP2 (Ad hTRP2/BM-DC or Ad mTRPZ BM-DC) were made using in vivo CTL and intracellular staining of IFN-γ(ICS), respectively. Additionally, the survival rate of immunized mice was checked after the subcutaneous inoculation with murine melanoma B16. F10 cells. Results: It was shown by in vivo CTL and ICS that, in the spleen, 6 h CTL killing and IFN-γ-producing CD8 ⁺ T cells in total CD8⁺ T cells induced by Ad hTRP2/BM-DC were (98.7 ± 1.2)% and (1.25 ± 0.21)% , respectively, whereas Ad mTRP2/BM-DC-induced 6 h CTL killing and IFN-γ-producing CD8⁺ T cells were just (28.6 ± 6.3)% and (0.24 ± 0.06)%, respectively. Moreover, 100% of the Ad hTRP2/BM-DC-immunized mice inoculated subcutaneously with 10⁶ B16. F10 cells were in a tumor-free state for three months, whereas only 40% of the Ad mTRP2/BM-DC-immunized mice with 5 × 10 ⁴ B16. F10 cells were survived. Conclusion: BM-DC modified with Ad hTRP2 breaks immune tolerance more effectively to murine melanomas and induces stronger immunity against melanomas as compared to BM-DC modified with Ad mTRP2, therefore acting as a highly effective dendritic cell-based tumor vaccine.