Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon Carcinoma

Abstract

Cancer immunotherapy emerged as a novel therapeutic approach to destroy tumor cells, and it has grown toward clinical transition following successful fundamental research and clinical trials. Immunotherapy by efficacious adjuvants is critical for increasing protective immune responses against infectious diseases and cancers. STING and TLR9 agonists are interesting candidates for novel immunotherapies of cancers. In this study, the antitumoral effects of ADU-S100, as a potent STING agonist, and CpG ODN1826, as a TLR9 agonist, in single and combined forms in CT-26 colon adenocarcinoma model were evaluated. This model was induced in female BALB/c mice which were divided into five groups treated with PBS, ADU-S100 (20 and 40 µg), CpG ODN (40 µg), and ADU-S100 (20 µg)+CpG ODN (20 µg). The tumor volumes and weights of mice were measured every other day. On the 30th day, the tumor, spleen, and liver tissues of mice were isolated for histopathological assessment. Hematological analysis was performed on heart blood. Intratumoral injection of agonists induced significant tumor suppression in all treatment groups with profound effect in the combination group that received half concentration of single form. Moreover, the histopathological analysis of tumor tissues showed the presence of apoptotic and inflammatory cells and increased the number of lymphocytes in the blood samples of the treatment groups indicating the effective role of these agonists in clearing the tumor. Therefore, a such synergy of adjuvants may have an effective role in cancer immunotherapy and offer new perspectives on the combination of agonists that trigger innate immune sensors during malignancy.

Keywords

• sting agonist
• tlr9 agonist
• synergistic effect
• immunotherapy
• colon carcinoma model