Therapeutic Effects of ADU-S۱۰۰ as STING Agonist and CpG ODN۱۸۲۶ as TLR۹ Agonist in CT-۲۶ Model of Colon Carcinoma

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 TLR۹ agonists are interesting candidates for novel immunotherapies of cancers. In this study, the antitumoral effects of ADU-S۱۰۰, as a potent STING agonist, and CpG ODN۱۸۲۶, as a TLR۹ agonist, in single and combined forms in CT-۲۶ colon adenocarcinoma model were evaluated. This model was induced in female BALB/c mice which were divided into five groups treated with PBS, ADU-S۱۰۰ (۲۰ and ۴۰ µg), CpG ODN (۴۰ µg), and ADU-S۱۰۰ (۲۰ µg)+CpG ODN (۲۰ µg). The tumor volumes and weights of mice were measured every other day. On the ۳۰th 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.

کلیدواژه ها:

STING agonist ، TLR۹ agonist ، Synergistic effect ، Immunotherapy ، Colon carcinoma model