Abstract
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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.