Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy

Abstract

Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING-TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology.

Sequential Delivery of Aptamer and STING Agonist Shuttled by Graphene Oxide

“…[10][11][12] While the reported drug delivery strategies have significant advantages in the treatment of primary tumors, they still face enormous challenges in deep or metastatic tumor therapy. [13][14][15] Moreover, realizing accurate and effective STING activation at the expected target and time also remains challenging. [16] In this study, taking advantage of the immunotherapy, the STING agonist and aptamer were grafted onto the GO (Apt/MSA2@GO), and STING agonist were targeting delivered to tumor cells under the action of aptamer.…”