ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Novel Quaternary Ammonium Salt-Linked STING Agonist Antibody-Drug Conjugate: Synergistic Activation of Tumor Immunity with Mitigated Off-Target Toxicity.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Article
- Pathogen-Centric Activation of an Azoreductase-Responsive Antibody-Antibiotic Conjugate for the Targeted Eradication of MRSA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A photodynamically activated nanoplatform relieves glucose-driven immunosuppression to potentiate STING immunotherapy in triple-negative breast cancer.Materials today. Bio · 2026Article
- Targeting DNA Damage Response and Immune Crosstalk in Cancer: Mechanistic Insights and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Novel Quaternary Ammonium Salt-Linked STING Agonist Antibody-Drug Conjugate: Synergistic Activation of Tumor Immunity with Mitigated Off-Target Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Immune-stimulating antibody conjugate (ISACs) incorporating STING agonists as payloads leverage both the targeting capability of the Fab region and the Fc region-mediated tumor antigen-dependent immune activation. Herein, a novel class of ISACs is reported, generated by engineering a quaternary ammonium-cleavable linker to conjugate diABZI STING agonist 3 (dSA3) with the HER2-targeting antibody Trastuzumab. The optimized ISAC (TZ-dSA3-12) demonstrated high potency, stability, enhanced solubility, and reduced off-target toxicity. The data showed that TZ-dSA3-12 potently activates the STING pathway in the tumor microenvironment through the synergistic action of the Fab and Fc regions of antibodies (activity switch-on). In contrast, TZ-dSA3-12 exhibited ≈75 fold lower activity than dSA3 in normal immune cells, where activation relies solely on the Fc region without Fab-mediated tumor antigen binding (activity switch-off). Furthermore, systemic administration of TZ-dSA3-12 at a dose (1 mg kg
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Registered trials
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