Co‐administration of carcinoembryonic antigen and HIV TAT fusion protein with CpG‐oligodeoxynucleotide induces potent antitumor immunity

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Abstract
Although dendritic cells (DC) have been well demonstrated as a strong cellular adjuvant for a tumor vaccine, there are several limitations for clinical application. A protein‐based vaccine using a potent adjuvant is an appealing approach for tumor antigen‐specific immunotherapy because of their simplicity, safety, efficacy and capacity for repeated administration. CpG‐oligodeoxynucleotides (ODN) have been used as adjuvants to stimulate innate and adaptive immune responses for cancer treatment. The authors evaluated the adjuvant effects of CpG‐ODN in a vaccine incorporating recombinant fusion protein of the HIV TAT PTD domain and carcinoembryonic antigen (TAT‐CEA). Mice vaccinated with TAT‐CEA and CpG‐ODN (TAT‐CEA + CpG) showed enhanced CEA‐specific immunity, including cytotoxic T‐lymphocytes (CTL) activity and interferon (IFN)‐γ secreting T cells compared with CEA and CpG‐ODN (CEA + CpG) or TAT‐CEA vaccination alone. Vaccination with TAT‐CEA + CpG elicited Th1‐based responses, as indicated by the higher ratio of immunoglobulin (Ig)G2a antibody/IgG1 antibodies specific for CEA. The survival rate was significantly increased after vaccination with TAT‐CEA + CpG in a tumor model using MC38/CEA2. Furthermore, the TAT‐CEA ± CpG vaccine groups showed similar antitumor immunity to the CEA peptide‐pulsed DC (CEA peptide/DC) vaccine groups. These data suggest that coadministration of TAT fusion protein with CpG‐ODN may serve as a potential formulation for enhancing antitumor activity. ( Cancer Sci 2008; 99: 1034–1039)

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