| First Author | McAndrews KM | Year | 2021 |
| Journal | J Biol Chem | Volume | 296 |
| Pages | 100523 | PubMed ID | 33711340 |
| Mgi Jnum | J:313270 | Mgi Id | MGI:6695515 |
| Doi | 10.1016/j.jbc.2021.100523 | Citation | McAndrews KM, et al. (2021) Effective delivery of STING agonist using exosomes suppresses tumor growth and enhances anti-tumor immunity. J Biol Chem :100523 |
| abstractText | The Stimulator of Interferon Genes (STING) pathway is implicated in the innate immune response and is important in both oncogenesis and cancer treatment. Specifically, activation of the cytosolic DNA sensor STING in antigen presenting cells (APCs) induces a type I interferon response and cytokine production that facilitates anti-tumor immune therapy. However, use of STING agonists (STINGa) as a cancer therapeutic has been limited by unfavorable pharmacological properties and targeting inefficiency due to rapid clearance and limited uptake into the cytosol. Exosomes, a class of extracellular vesicles shed by all cells, are under consideration for their use as effective carriers of drugs owing to their innate ability to be taken up by cells and their biocompatibility for optimal drug biodistribution. Therefore, we engineered exosomes to deliver the STING agonist cyclic GMP-AMP (iExo(STINGa)), to exploit their favorable pharmacokinetics and pharmacodynamics. Selective targeting of the STING pathway in APCs with iExo(STINGa) was associated with superior potency compared to STINGa alone in suppressing B16F10 tumor growth. Moreover, iExo(STINGa) showed superior uptake of STINGa into dendritic cells compared to STINGa alone, which led to increased accumulation of activated CD8(+) T-cells and an anti-tumor immune response. Our study highlights the potential of exosomes in general, and iExo(STINGa) specifically, in enhancing cancer therapy outcomes. |
