Dendritic cells modified with 6Ckine/IFNgamma fusion gene induce specific cytotoxic T lymphocytes in vitro.

Background And Objective: [corrected] Dendritic cells play an important role in initiation and regulation of immune responses. Previous studies demonstrated that intratumoral administration of 6Ckine-modified DCs enhanced local and systemic antitumor effects. Herein we report the investigation of the specific CTL responses elicited by adenoviral 6Ckine/IFNgamma fusion gene-modified DCs in vitro.

Methods: Human monocyte-derived DCs were modified with an adenoviral vector encoding 6Ckine/IFNgamma fusion protein (Ad-6Ckine/IFNgamma), and then investigated the effect of 6Ckine/IFNgamma fusion protein on the maturation, cytokine and chemokine secretion of DCs, and their activities of recruiting and activating T cells in vitro were investigated.

Results: 6Ckine/IFNgamma fusion protein induced DC maturation characterized with the upregulation of CD83 and CCR7. And it up-regulated the expression of RANTES and IL-12p70, down-regulated that of IL-10 in DCs. Additionally, 6Ckine/IFNgamma markedly increased DC's recruiting ability for naive T cells, benefiting from the enhanced expression of chemokines 6Ckine and RANTES in DCs. Fusion gene-modified DCs significantly promoted the proliferation of autologous T cells, induced Th1 differentiation by upregulating the expression of IL-2 and T-bet in T cells, and increased specific cytotoxicity of CTLs against specific tumor cells, HepG2 or LoVo cells, respectively.

Conclusion: Combining the effects of 6Ckine and IFNgamma, Ad-6Ckine/IFNgamma modified DCs induced enhanced CTL responses in vitro, which indicated that Ad-6Ckine/IFNgamma modified DCs might be used as an adjuvant to trigger an effective antitumor immune response.