Definition

Exosomes containing an agonist of the stimulator of interferon genes protein (STING; transmembrane protein 173; TMEM173) and expressing high levels of the exosome surface glycoprotein prostaglandin F2 receptor negative regulator (PTGFRN; CD315), with potential immunoactivating and antineoplastic activities. Upon intratumoral administration, STING agonist-containing PTGFRN-expressing exosomes CDK002 preferentially targets and binds to STING on antigen-presenting cells (APCs), specifically monocytes and M2 macrophages, in the tumor microenvironment (TME) and activates the STING pathway. This leads to the activation of the innate immune response locally and results in the production of pro-inflammatory cytokines, including interferons (IFNs), enhances the cross-presentation of tumor-associated antigens (TAAs) by dendritic cells (DCs), and induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. STING, a transmembrane protein that activates immune cells in the TME, plays a key role in the activation of the innate immune system. The exosome-based formulation may provide targeted anti-tumor immunity while minimizing off-target toxicity, including the toxic systemic cytokine elevation. PTGFRN, expressed on the surface of the exosome, facilitates specific uptake in tumor-resident APCs and enhances the APC-mediated systemic anti-tumor immune response.