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

Dazostinag, combined with pembrolizumab after radiotherapy, was well tolerated and demonstrated clinical activity in some patients with advanced/metastatic tumors whose disease had progressed on CPIs.

P1, N=21, Completed, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Recruiting --> Completed | N=30 --> 21

P1, N=6, Completed, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Recruiting --> Completed | N=30 --> 6

Candidates such as ADU-S100 and MSA-2 demonstrate enhanced STING activation and clinical potential...Future directions emphasize the development of smart nanocarriers with spatiotemporal control, biomarker-driven patient stratification, and combinatorial regimens that integrate epigenetic or metabolic modulators. This review underscores the transformative potential of cGAS-STING-targeted therapies while outlining critical hurdles and interdisciplinary strategies to advance precision cancer immunotherapy.

The stochastic cysteine conjugation of the dazostinag containing these linkers provided ADC TAK-500 and its mouse surrogate mTAK-500 with DAR = 4. In syngeneic tumor-bearing mouse models, mTAK-500 showed target specific antitumor activity as well as the induction of immune-stimulating cytokines.

NanoSTING@Mn, composed of ADU-S100 complexed with Mn2⁺ and encapsulated in biomimetic liposomes, potently activates the cGAS-STING pathway, induces a type I interferon response, and promotes lymphocyte infiltration...Upon intravenous rechallenge, disseminated tumor cells are eliminated, preventing metastasis and ensuring long-term protection. This synergistic approach offers a scalable platform to boost immunotherapy efficacy and redefines immune-based metastasis prevention strategies.

P1, N=10, Terminated, Actym Therapeutics, Inc. | N=35 --> 10 | Trial completion date: Jul 2026 --> Aug 2025 | Recruiting --> Terminated | Trial primary completion date: Jan 2026 --> Aug 2025; Sponsor's strategic business decision

Targeting polyamine biosynthesis reverses IRF3 down-regulation, restoring sensitivity to STING agonists in MTAP-deficient tumors. Our findings suggest that MTAP genetic status may inform patient responses to STING agonist therapy and offer an alternative strategy for boosting antitumor immune responses using STING agonists in MTAP-deleted tumors.

P1, N=6, Active, not recruiting, University of Maryland, Baltimore | Recruiting --> Active, not recruiting | N=36 --> 6

Single-cell RNAseq and flow cytometry data confirmed activation and infiltration of both innate and adaptive immune cells. ACTM-838 showed durable anti-tumor efficacy in multiple murine tumor models and synergized with anti-PD1 therapy in combination.