Abstract
CD40L, the ligand for CD40 on dendritic cells (DCs), plays an important role in their activation and is essential for induction of antigen-specific T-cell responses. In the present study, we investigated the efficacy of antitumor immunity induced by vaccination with DCs engineered to express CD40L and pulsed with Mut1 tumor peptide. Our data show that transfection of DCs with recombinant adenovirus AdV-CD40L resulted in activation of DCs with up-regulated expression of proinflammatory cytokines (IL-1β and IL-12), chemokines (RANTES, IP-10, and MIP-1α), and immunologically important cell surface molecules (CD54, CD80, and CD86). Our data also demonstrate that DCs transfected with AdV-CD40L (DCCD40L) are able to stimulate enhanced allogeneic T-cell proliferation and Mut1-specific CD8+ cytotoxic T-cell responses in vitro. Vaccination of mice with Mut1 peptide-pulsed control virus–transfected DC (DCpLpA) could only protect mice from challenge of a low dose (0.5×105 cells per mouse, 8/8 mice), but not a high dose (3×105 cells per mouse, 0/8 mice) of 3LL tumor cells. However, vaccination of Mut1 peptide-pulsed AdV-CD40L–transfected DCCD40L induced an augmented antitumor immunity in vivo by complete protection of mice (8/8) from challenge of both low and high doses of 3LL tumor cells. Thus, DCs engineered to express CD40L by adenovirus-mediated CD40 ligand gene transfer may offer a new strategy in production of DC cancer vaccines.
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This work was supported by a research grant (ROP-15151) of the Canadian Institute of Health Research.
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Liu, Y., Zhang, X., Zhang, W. et al. Adenovirus-mediated CD40 ligand gene-engineered dendritic cells elicit enhanced CD8+ cytotoxic T-cell activation and antitumor immunity. Cancer Gene Ther 9, 202–208 (2002). https://doi.org/10.1038/sj.cgt.7700429
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DOI: https://doi.org/10.1038/sj.cgt.7700429
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