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Updated: Nov 8, 2025

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
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Published on: September 23, 2021

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

Su Chul Jang1, Kyriakos D Economides1, Raymond J Moniz1

  • 1Codiak BioSciences Inc., Cambridge, MA, USA.

Communications Biology
|April 23, 2021
PubMed

Insights

Engineered extracellular vesicles loaded with cyclic dinucleotides (CDNs) called exoSTING enhance anti-tumor immunity. This novel therapy improves STING pathway activation, generating systemic immunity without causing inflammation.

Area of Science:

  • Immunology
  • Oncology
  • Nanomedicine

Background:

  • Cyclic dinucleotides (CDNs) activate the STING pathway for anti-tumor immunity.
  • Intratumoral CDN delivery causes TME cytotoxicity, systemic inflammation, and immune ablation, limiting efficacy.
  • Current CDN therapies fail to establish long-term immunological memory.

Purpose of the Study:

  • To develop a novel therapeutic that enhances CDN potency and delivery for improved anti-tumor immunity.
  • To investigate the efficacy of exoSTING, an engineered extracellular vesicle (EV) loaded with CDN.
  • To evaluate exoSTING's impact on the tumor microenvironment (TME) and systemic immune responses.

Main Methods:

  • Exogenous loading of CDN into engineered EVs (exoSTING).
  • Intratumoral injection of exoSTING in pre-clinical tumor models.
  • Analysis of TME cellular composition, immune cell recruitment (CD8+ T cells), and cytokine profiles.
  • Assessment of systemic anti-tumor immunity and therapeutic window.

Main Results:

  • ExoSTING enhanced CDN potency and preferentially activated antigen-presenting cells in the TME.
  • Intratumoral exoSTING was retained, boosting local Th1 responses and CD8+ T cell infiltration.
  • ExoSTING generated systemic anti-tumor immunity and demonstrated a favorable therapeutic window without systemic inflammation.

Conclusions:

  • ExoSTING leverages EV biology for enhanced CDN activity and targeted STING pathway activation.
  • ExoSTING represents a novel therapeutic candidate with improved efficacy and safety for cancer immunotherapy.
  • This approach overcomes limitations of conventional CDN delivery, promoting durable anti-tumor immunity.

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