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Potentiation of a Dendritic Cell Vaccine for Murine Renal Cell Carcinoma by CpG Oligonucleotides

¹ Department of Surgery (Urology), McGill University, Montreal, Quebec, Canada and ² Department of Pathology, Baylor College of Medicine, Houston, Texas

Requests for reprints: Simon Tanguay, 1650 Cedar Avenue, L8-309 Montreal, Quebec, H3G 1A4 Canada. Phone: 514-934-8295; Fax: 514-934-8297; E-mail: stangu{at}po-box.mcgill.ca.

Purpose: An ideal vaccine therapy for tumors should activate both effector and memory immune responses against tumor-specific antigens. Here we investigated the effect of CpG oligodeoxynucleotides (CpG-ODN) for their ability to potentiate the activity of tumor antigen–pulsed bone marrow–derived dendritic cells (DC) in a vaccine model for the treatment of murine renal cell carcinoma (RENCA).

Experimental Design: First we evaluated the effects of a murine renal cell carcinoma (RENCA) on immune cell activity in a mouse model using in vitro assays for T-cell proliferation and natural killer cell activation. To overcome the immune suppression of the tumor, we s.c. injected groups of 10 mice with dendritic cells and tumor cells. We compared the effect of different conditioning regimens of the DCs with RENCA antigen and/or CpG-ODNs before injection by measuring tumor size twice a week.

Results: Tumor growth was shown to negatively affect spleen cell and T-cell proliferation, IFN- production, natural killer cell activity, and NF-B activation in T cells. In this model, we have shown that RENCA-pulsed CpG-ODN-treated DCs were able not only to significantly reduce tumor growth but also to prevent tumor implantation in 60% of mice. Tumor-free mice were resistant to tumor challenge and the immunity conferred by the vaccine was transferable and tumor specific.

Conclusions: This data show that RENCA down-modulates the immune response, and DC vaccine therapy, in conjunction with CpG-ODN, can restore tumor-specific immunity.

Key Words: murine tumors • immune therapy • bacterial DNA motifs