Unmethylated
cytosine-phosphorothioate-guanine (CpG) containing
oligodeoxynucleotides (
CpG-ODN) are known to act as adjuvants and powerful activators of the innate immune system. We investigated the
therapeutic effect of
CpG-ODN on a variety of established mouse
tumors including AG104A, IE7
fibrosarcoma,
B16 melanoma, and 3LL lung
carcinoma. These
tumors are only weakly immunogenic and notoriously difficult to treat. Repeated peritumoral injection of
CpG-ODN resulted in complete rejection or strong inhibition of
tumor growth, whereas systemic application had only partial effects. The
CpG-ODN-induced
tumor rejection was found to be mediated by both NK and
tumor-specific CD8(+) T cells. Comparison of parental
tumors and variants rendered more antigenic by transfection with
tumor Ags suggested that the efficiency of the
CpG-ODN therapy correlated with the antigenicity of the
tumors. Peritumoral
CpG-ODN treatment was even effective in a situation where the immune system was tolerant for the
tumor Ag, as shown by breakage of tolerance and
tumor elimination. These results suggest that peritumoral application of
CpG-ODN acts locally by inducing NK cells, and also leads to efficient presentation of
tumor Ags and stimulation of CD8(+) effector and memory T cells, thus providing a powerful antitumor
therapy that can be also applied without knowledge of the
tumor Ag.