In vivo, host STING activation with cGAMP-VLP improves the efficacy of immune checkpoint blockade, particularly in tumors lacking cGAS. Together, these findings identify a transcellular mechanism whereby STING activation in dendritic cells increases tumor cell MHC-I expression to enhance CD8+ T cell-mediated tumor recognition.

Using a syngeneic mouse model of genetically engineered Egfr-mutant NSCLC, we evaluated the antitumor effects of STING agonist ADU-S100, alone and combined with osimertinib. Crucially, the combination induced an abscopal effect accompanied by PD-1+/CD8+ cell infiltration. Combining osimertinib with a STING agonist augmented innate and adaptive immunity, inducing systemic antitumor responses in EGFR-mutant NSCLC.

P1, N=12, Not yet recruiting, Daiichi Sankyo Inc.

P1/2, N=248, Completed, Takeda | Active, not recruiting --> Completed

TAK-500 is a novel immune cell-directed antibody-drug conjugate (iADC) composed of TAK-202, an anti-CCR2 monoclonal antibody, conjugated to the STING agonist dazostinag (TAK-676), and is designed to stimulate antitumor immunity by reprogramming CCR2-positive monocytes. These findings demonstrate the feasibility of predicting TAK-500 PK and RO in humans by integrating preclinical and parental antibody clinical data, providing a quantitative framework for first-in-human dose selection of immune cell-directed ADCs. Trial Registration: Clinical trials: NCT04420884, NCT04879849.

P1, N=6, Suspended, University of Maryland, Baltimore | Active, not recruiting --> Suspended | Trial primary completion date: Jan 2026 --> Aug 2025

This study clarified the mechanism underlying the potent antitumor activity of SR-717 in nervous system tumors through activation of the STING-STAT1-HMGN2 signaling pathway and demonstrated that SR-717 has superior efficacy compared to E7766. In addition, HMGN2 was shown to exhibit translational potential as a prognostic biomarker for patient survival.

P1, N=97, Active, not recruiting, GlaxoSmithKline | Trial completion date: Mar 2025 --> Mar 2026

To address these limitations, we have engineered cationic quaternary ammonium salt-based drug-eluting microspheres capable of loading 131I and ADU-S100...This approach effectively overcomes the current limitations of poor embolic efficacy and non-target embolization associated with radioactive microspheres. Moreover, it activates the tumor immune microenvironment, addressing the issue of tumor immune resistance and further improving therapeutic outcomes, thereby showing great clinical application potential.

Activation of STING pathway by ADU-S100 enhances the antitumor efficacy of doxorubicin in STS. Combining doxorubicin with STING agonists may be a promising therapeutic strategy worth exploring in future clinical trials.

In HCC models with liver fibrosis in male mice, anti-PD-1 ICB or the STING agonist BMS-986301 increase intratumoral B-cell infiltration, circulating IL-10, and TIM-1+ B-cells, promoting tertiary lymphoid structure formation...In addition, co-targeting STING and TIM-1 enhances B-cell differentiation and antigen presentation, reduces intratumoral TIM-1+ B-cells, and increases CD86 and MHC class II expression, thereby augmenting CD8+ T-cell-mediated anti-tumor immunity. These findings reveal that B-cells contribute to ICB and STING therapy resistance in HCC, and that B-cell depletion or TIM-1 blockade can overcome acquired resistance to these immunotherapies.

P1, N=70, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting