Adenovirus-mediated cd40 ligand gene-engineered dendritic cells elicit enhanced cd8+ cytotoxic t-cell activation and antitumor immunity

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. Access through your institution Buy or subscribe

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DENDRITIC CELL VACCINE FOR BOTH VACCINATION AND NEOANTIGEN-REACTIVE T CELL PREPARATION FOR CANCER IMMUNOTHERAPY IN MICE Article Open access 29 November 2024 EXPANDING CROSS-PRESENTING

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This work was supported by a research grant (ROP-15151) of the Canadian Institute of Health Research. AUTHOR INFORMATION Author notes * Yongqing Liu and Xuishu Zhang: Y Liu and X Zhang made

the same contribution to this manuscript. AUTHORS AND AFFILIATIONS * 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 * Department of Biochemistry, Queen's

University, Kingston, K7L 3N6, Ontario, Canada Zongchao Jia Authors * Yongqing Liu View author publications You can also search for this author inPubMed Google Scholar * Xuishu Zhang View

author publications You can also search for this author inPubMed Google Scholar * Weidong Zhang View author publications You can also search for this author inPubMed Google Scholar * Zhuang

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Kaiser Ali View author publications You can also search for this author inPubMed Google Scholar * Zongchao Jia View author publications You can also search for this author inPubMed Google

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permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 20 November 2001 * Published: 18 February 2002

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Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * engineered dendritic

cell vaccine * adenoviral vector * CD40 ligand * antitumor immunity