2. Academic Validation
  3. ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance

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

  • Commun Biol. 2021 Apr 22;4(1):497. doi: 10.1038/s42003-021-02004-5.
Su Chul Jang 1,  Kyriakos D Economides 1,  Raymond J Moniz 1,  Chang Ling Sia 1,  Nuruddeen Lewis 1,  Christine McCoy 1,  Tong Zi 1,  Kelvin Zhang 1,  Rane A Harrison 1,  Joanne Lim 1,  Joyoti Dey 2,  Marc Grenley 2,  Katherine Kirwin 1,  Nikki L Ross 1,  Raymond Bourdeau 1,  Agata Villiger-Oberbek 1,  Scott Estes 1,  Ke Xu 1,  Jorge Sanchez-Salazar 1,  Kevin Dooley 1,  William K Dahlberg 1,  Douglas E Williams 1,  Sriram Sathyanarayanan 3
Affiliations

Affiliations

  • 1 Codiak BioSciences Inc., Cambridge, MA, USA.
  • 2 Presage Biosciences, Seattle, WA, USA.
  • 3 Codiak BioSciences Inc., Cambridge, MA, USA. sriram.sathy@codiakbio.com.
PMID: 33888863 DOI: 10.1038/s42003-021-02004-5
Abstract

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

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