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Adenovirus-mediated CD40 ligand gene-engineered dendritic cells elicit enhanced CD8+ cytotoxic T-cell activation and antitumor immunity

Cancer Gene Therapy volume 9, pages 202–208 (2002)Cite this article

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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Acknowledgements

This work was supported by a research grant (ROP-15151) of the Canadian Institute of Health Research.

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  1. Yongqing Liu and Xuishu Zhang: Y Liu and X Zhang made the same contribution to this manuscript.

Authors and Affiliations

  1. Saskatchewan Cancer Agency and Departments of Oncology and Pathology, Research Unit, College of Medicine, University of Saskatchewan, Saskatoon, S7N 0W0, Saskatchewan, Canada

    Yongqing Liu, Xuishu Zhang, Weidong Zhang, Zhuang Chen, Tim Chan, Kaiser Ali & Jim Xiang

  2. Department of Biochemistry, Queen's University, Kingston, K7L 3N6, Ontario, Canada

    Zongchao Jia

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Correspondence to Jim Xiang.

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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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