Development of new cancer immunotherapy using activation of Toll like receptor against gastrointestinal cancer

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CpG oligodeoxynucleotides (CpG-ODNs) mimic bacterial DNA and induce immune response that comprise innate immunity and acquired Th-1 biased cellular immunity. Recently, 3 types of CpG-ODNs (CpG-A, CpG-B and CpG-C) have been identified based on distinct immunologic activities on human plasmacytoid dendritic cells (PDCs) and B cells. We investigated the activity of these three types of CpG-ODN to enhance the induction of peptide specific CTLs. First, human PBMCs of healthy volunteers were stimulated with each types of CpG-ODN for 48 hours. Samples of the culture media were analyzed for cytokine induction with ELISA method. CpG-A and CpG-C, but not CpG-B, were potent inducers of IFN-α. Second, Flu peptide-specific CTLs were generated from PBMCs cultured with Flu peptide and each types of CpG-ODN for 2 weeks to compare the lytic activity against A24-LCL cells pulsed with Flu peptide in a standard Cr lysis assay. Flu peptide-specific cytotoxicity was enhanced in the presence of each type of CpG-ODN and especially CpG-A and CpG-C showed higher lytic activity than CpG-B. This CpG ODN-induced enhancement of cytotoxicity was disappeared when PDCs were depleted from PBMCs. In conclusion, our results showed that CpG-A and CpG-C might be the superior vaccine adjuvant to CpG-B at least in vitro.