Abstract 481: Oligodeoxynucleotides expressing Poly-G motifs promote anti-tumor activity through the up-regulation of IL-2.

The primary goal of cancer immunotherapy is to elicit an immune response capable of eliminating the tumor. One approach towards accomplishing that goal utilizes general (rather than tumor-specific) immunomodulatory agents to boost the number and activity of pre-existing cytotoxic T lymphocytes. We find that the intra-tumoral injection of poly-G ODN has such an effect, boosting anti-tumor immunity and promoting tumor regression. The anti-tumor activity of poly-G ODN was mediated through CD8 T cells in a TLR9 independent manner. Mechanistically, poly-G ODN directly induced the phosphorylation of Lck (an essential element of the T cell signaling pathway), thereby enhancing the production of IL-2 and CD8 T cell proliferation. These findings establish poly-G ODN as a novel type of cancer immunotherapy. Citation Format: Nobuaki Kobayashi, Dennis M. Klinman, Masahiro Sasaki, Takeshi Kaneko, Yoshiaki Ishigatsubo, Hidekazu Shirota. Oligodeoxynucleotides expressing Poly-G motifs promote anti-tumor activity through the up-regulation of IL-2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 481. doi:10.1158/1538-7445.AM2013-481