ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance

• DOI: 10.1038/s42003-021-02004-5
• Publication Date: 2021-04-22T10:10:11Z
• Authors: Su Chul Jang; Kyriakos D. Econo...; Raymond J. Moniz; Chang Ling Sia; Nuruddeen Lewis; Christine McCoy; Tong Zi; Kelvin Zhang; Rane A. Harrison; Joanne Lim; Joyoti Dey; Marc Grenley; Katherine Kirwin; Nikki L. Ross; Raymond Bourdeau; Agata Villiger-Ob...; Scott Estes; Ke Xu; Jorge Sanchez-Sal...; Kevin Dooley; William K. Dahlberg; Douglas E. Williams; Sriram Sathyanara...
• Keywords: Sting; Extravasation

Abstract Cyclic dinucleotide (CDN) agonists of the STimulator InterferoN Genes (STING) pathway have shown immune activation and tumor clearance in pre-clinical models. However, CDNs administered intratumorally also promote STING leading to direct cytotoxicity many cell types microenvironment (TME), systemic inflammation due rapid extravasation CDN, ablation TME. These result a failure establish immunological memory. ExoSTING, an engineered extracellular vesicle (EV) exogenously loaded with enhances potency CDN preferentially activates antigen presenting cells Following intratumoral injection, exoSTING was retained within tumor, enhanced local Th1 responses recruitment CD8 + T cells, generated anti-tumor immunity tumor. ExoSTING at therapeutically active doses did not induce inflammatory cytokines, resulting therapeutic window. is novel, differentiated candidate that leverages natural biology EVs enhance activity CDNs.