Eradication of tumors and development of anti-cancer immunity using STINGa targeted by pHLIP.

ABSTRACT: Despite significant progress in the development of novel STING agonists (STINGa), applications appear to be challenged by the low efficiency and poor selectivity of these agents. A pH Low Insertion Peptide (pHLIP) extends the lifetime of a STINGa in the blood and targets it to acidic cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid derived suppressor cells (mMDSCs) and dendritic cells (DCs). CAFs constitute 25% of all live cells within CT26 tumors, and M2-type TAMs and mMDSCs are the most abundant among the immune cells. The resulting activation of cytokines within the tumor microenvironment (TME) triggers the eradication of small (100 mm³) and large (400-700 mm³) CT26 tumors in mice after a single dose of pHLIP-STINGa. The tumor stro

SUBMITTER: Moshnikova A 

PROVIDER: S-EPMC9622777 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature