Stimulatory effects of CpG oligodeoxynucleotide on dendritic cell-based immunotherapy of colon cancer in CEA/HLA-A2 transgenic mice†
Version of Record online: 19 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 124, Issue 4, pages 877–888, 15 February 2009
How to Cite
Saha, A., Bhattacharya-Chatterjee, M., Foon, K. A., Celis, E. and Chatterjee, S. K. (2009), Stimulatory effects of CpG oligodeoxynucleotide on dendritic cell-based immunotherapy of colon cancer in CEA/HLA-A2 transgenic mice. Int. J. Cancer, 124: 877–888. doi: 10.1002/ijc.24009
This study was presented as an abstract at the 94th Annual Meeting of the AAI, May 18–22, 2007, Miami Beach, FL.
- Issue online: 11 DEC 2008
- Version of Record online: 19 SEP 2008
- Accepted manuscript online: 19 SEP 2008 12:00AM EST
- Manuscript Accepted: 28 AUG 2008
- Manuscript Received: 13 JUN 2008
- NIH. Grant Number: RO1 CA104804
- dendritic cells;
- CpG ODN;
- CTL epitope;
- anti-idiotype antibody;
- CEA-A2Kb double transgenic mice;
- antigen presenting cells
Immunostimulatory DNA containing unmethylated cytosine-guanine (CpG) motifs have been successfully used as adjuvants to enhance the immunity of vaccines designed to trigger antitumor T-cell responses. We examined the effect of a CpG oligodeoxynucleotide (CpG ODN) for its ability to potentiate the activity of tumor antigen-pulsed dendritic cells (DC) in a clinically relevant mouse model, which is transgenic for both carcinoembryonic antigen (CEA) and HLA-A2 for the treatment of colon carcinoma in a therapeutic setting. The systemic administration of CpG ODN 1826 alone had modest effect on tumor growth when tumors were palpable and had no effect with larger tumor burden. However, coadministration of CpG ODN 1826 with the vaccine provided significant increase in tumor-free survival compared with mice immunized with DC-based vaccines alone. The DC/CpG combined vaccination strategy resulted in increased secretion of Th1 cytokines and HLA-A2-restricted CEA-specific CTL responses were also enhanced. Both tumor regression and extended tumor-free survival resulting from DC/CpG combination therapy required the participation of T cells. Tumor-free mice were resistant to tumor rechallenge and immunity conferred by the vaccine was transferable in athymic nude mice. These results provide evidence that vaccination with antigen-pulsed DC with CpG ODN as adjuvant can lead to effective tumor regression and long-term survival in a murine model of colon carcinoma. © 2008 Wiley-Liss, Inc.