ADU-S100 / Novartis - LARVOL DELTA

Mitochondrial DNA released by Biliary Epithelial Cells enhances inflammation in Biliary Atresia through the cGAS-STING-NF-κB pathway. (PubMed, Cell Mol Gastroenterol Hepatol) - "mtDNA leakage activates the cGAS-STING-NF-κB pathway in BECs, driving a CXCL10/IL-32-dominant inflammatory response. CoQ10 mitigates this process and injury, supporting cGAS-STING modulation and mitochondrial stabilization as promising therapeutic strategies for BA."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Rotavirus Infections • CGAS • CK19 • CXCL10 • IL32 • KRT19 • STING

SMPDM3B-loaded extracellular vesicles from tumor-associated macrophages drive ovarian cancer chemoresistance by inhibiting the cGAS/STING pathway. (PubMed, Arch Biochem Biophys) - "Chemoresistance of OC cell lines were evaluated after treated with cisplatin...Mechanistically, SMPDL3B upregulation in OC cells increased chemoresistance by inhibiting the cGAS/STING pathway, and the pathway activator ADU-S100 reversed its effect...Finally, the xenograft model showed that TAMs co-injection promoted tumor progression, whereas SMPDL3B knockdown in TAMs abolished this effect. Collectively, this study demonstrates that TAMs-derived EVs transfer SMPDL3B to OC cells, where it inhibits the cGAS/STING pathway and thereby enhances chemoresistance."

Journal • Oncology • Ovarian Cancer • Solid Tumor

AMnESTI reverses age-associated lung immune decline to drive heterosubtypic protection by inactivated influenza vaccines. (PubMed, Sci Immunol) - "We developed AMnESTI (AEC-targeting MN Encapsulated STING agonist), an alveolar epithelial cell (AEC)-targeting manganese-complexed liposome encapsulating the stimulator of interferon genes (STING) agonist ADU-S100...A single intranasal dose of AMnESTI-adjuvanted influenza vaccine conferred complete heterosubtypic protection in aged mice against representative influenza strains. These findings demonstrate that transient reprogramming of aged lung immunity facilitates robust vaccine responses and identify AECs as a potential mucosal adjuvant target for broadly protective influenza vaccines in the elderly."

Journal • Infectious Disease • Influenza • Respiratory Diseases • CGAS • STING

Astrocytic TRPC6 protects against cerebral ischemia-reperfusion injury by inhibiting cGAS-STING pathway. (PubMed, Exp Neurol) - "Astrocytic TRPC6 maintains BBB integrity by negatively regulating the cGAS-STING innate immune pathway in the early phase of CIRI. The study identified the "Astrocyte TRPC6-STING-Tight Junction" axis, offering a precise and promising novel therapeutic target for CIRI."

Journal • Cardiovascular • Inflammation • Reperfusion Injury • AQP4 • GFAP • OCLN • TJP1 • TRPC6

Stepwise Enhancement of HPV16 E6/E7 mRNA Vaccine Efficacy Using HSV-1 gD Epitope Incorporation and Immune-Modulating Agents. (PubMed, Res Sq) - "Antitumor efficacy, antigen-specific T-cell responses, and tumor immune infiltration were assessed following vaccination alone or in combination with the histone deacetylase (HDAC) inhibitor entinostat or the STING agonist ADU-S100, two immunomodulatory agents known to remodel the tumor microenvironment. These findings demonstrate that incorporation of a heterologous HSV-1 gD helper epitope can augment HPV E6/E7-targeted mRNA vaccination by harnessing pre-existing HSV-1-specific immune memory and enhancing CD4⁺ T-cell help. Together with ubiquitin-mediated enhancement of antigen presentation and modulation of the tumor microenvironment through HDAC inhibition or STING activation, these complementary potentiation strategies may further improve therapeutic outcomes and support the development of combinatorial immunotherapeutic approaches for HPV-associated cancers."

Journal • Herpes Simplex • Infectious Disease • Oncology • Targeted Protein Degradation • CD4 • CD8

Activation-induced SLC7A1 expression enhances T cell sensitivity to cGAMP-mediated STING signaling. (PubMed, Cell Rep) - "We identified distinct residues in SLC7A1 that mediate cGAMP and arginine activity, suggesting that cGAMP transport may be separable from arginine uptake. These findings suggest that modulation of SLC7A1 may influence T cell susceptibility to cGAMP and its analogs."

Journal • Oncology • STING

Chemically Regulated STING-Activating Prodrugs of Deoxyribose Cyclic Dinucleotides Elicit Robust Immune Activation and Durable Antitumor Immunity. (PubMed, Angew Chem Int Ed Engl) - "In murine models, prodrugs elicited significantly stronger stimulation in the development of an antitumor immune response compared to the parent CDN 3',3'-c-di-dAMP, as well as the clinically relevant STING agonist ADU-S100. The (Rp,Rp) diastereoisomer exhibited the most pronounced antitumor activity in the context of intravenous administration, significantly suppressing tumor proliferation, extending the survival with a complete response (CR) rate of 90% in a mouse CT26 tumor model, and establishing long-lasting tumor-specific immunological memory. These findings underscore the importance of considering the chirality of phosphotriesters in the development of more effective, safer, and sustainable STING agonist in tumor immunotherapy."

Journal • Oncology • GLI2 • STING

Targeting mitochondria to activate immunity against multiple myeloma (EACR 2026) - "Interestingly, we observed that treatment with the STING agonist ADU-S100 induces a significantly weaker IFN-I response in MM cells compared to THP1, a monocytic leukemia cell line... This project will investigate novel mitochondrial vulnerabilities in MM cells to offer new actionable targets and broaden the therapeutic arsenal against this tumor. Targeting mitochondrial homeostasis may represent a novel approach to couple a direct cytotoxic effect together with immunogenic stimulus."

IO biomarker • Hematological Malignancies • Leukemia • Multiple Myeloma • GLI2

Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in Egfr-mutated lung cancer. (PubMed, Mol Oncol) - "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."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • EGFR • PD-1 • STING

Harnessing STING Activation to Overcome Immune Suppression in Glioblastoma (ASGCT 2026) - "STING signaling was activated using synthetic cyclic dinucleotide agonists (e.g., ADU-S100), administered alone or in combination with the G47Δ oncolytic herpes simplex virus (oHSV)...In contrast, infection with the oncolytic herpes simplex virus G47Δ (2) interferes with cGAS- STING signaling, counteracting pathway activation while promoting tumor cell lysis and immune modulation. Created in BioRender"

IO biomarker • Brain Cancer • Glioblastoma • Herpes Simplex • Immune Modulation • Immunology • Infectious Disease • Solid Tumor • CGAS • CXCL10 • IFNB1 • STING

cGAS-STING Signalling in the tumour microenvironment: Implications for immune surveillance and therapeutic strategies. (PubMed, Int Immunopharmacol) - "Pharmacological activation using cyclic dinucleotides (CDN) STING agonists (ADU-S100 and MK-1454) and non-CDN STING agonists (diABZI and MSA-2), as well as MPS1 inhibitors (CFI-402257, BAY-1217389, and CC-671), has effectively triggered strong type I interferon responses and caused tumour regression in preclinical and clinical trials. When combined with radiotherapy, PARP inhibitors, or immune checkpoint blockers, these agents exhibit enhanced synergy but are constrained by tumour heterogeneity and context-dependent toxicity. Here, we reviewed the complexity of the cGAS-STING and its potential as a double-edged sword in cancer treatment, underscoring the need for strict strategies to harness this pathway while enhancing antitumour immunity and mitigating pro-tumorigenic effects."

Journal • Review • Fibrosis • Immunology • Oncology • CGAS • STAT3 • STING • TGFB1

cGAS-STING pathway agonist plus immune checkpoint inhibitor augments chemotherapy effectiveness in murine osteosarcoma models (AACR 2026) - "At day 40 post-tumor challenge, 46% of the ADU-S100 + carboplatin + ICI treated mice continue with disease control compared to 9% in the ADU-S100 + carboplatin treated cohort (P=0.035). Ongoing studies include combining ADU-S100 + ICI with doxorubicin, cisplatin, and methotrexate (standard of care chemotherapy agents given for OS in humans) and investigations of the mechanisms determining responder versus non-responder mice."

Checkpoint inhibition • Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CXCL10 • IFNB1 • IL6 • TNFA

Rewiring the dendritic cell: Regulatory T cell axis sensitizes prostate cancer to immunotherapy (AACR 2026) - P1 | "To investigate responses to Treg depletion (via FcE-αCTLA-4) alongside DC expansion (via Flt3L-Ig) and stimulation (via STING agonist ADU-S100) in PCa, we employed the castration-sensitive MycCaP PCa model and 45-parameter spectral flow cytometry... DC insufficiency and effector Treg differentiation are hallmarks of advanced PCa. Enhancing DC number and function concomitant with Treg depletion can drive effective antitumor immunity in a pre-clinical PCa model. Direct DC modulation via FcγR engagement represents a novel mechanism of response to CTLA-4-targeted ICB."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CDK1 • FCER1G • TNFRSF9

NanoSTING@Mn Reprograms Aged Lung Immunity to Unleash the Potential of Universal Influenza Vaccines (IMMUNOLOGY 2026) - "To address this, we targeted alveolar epithelial cells (AECs) to reprogram the aged lung microenvironment and robustly enhance vaccine efficacy. We developed nanoSTING@Mn, a pulmonary surfactant-biomimetic liposome encapsulating the pan-STING agonist, ADU-S100 complexed with manganese, aimed to activate the cGAS-STING pathway in AECs... The study demonstrates, for the first time, that targeted activation of the cGAS–STING pathway in AECs can reverse age-associated immune dysfunction by reorienting myeloid lineage differentiation. NanoSTING@Mn thereby achieves youthful-like vaccine efficacy in aged hosts—an outcome unattainable with conventional TLR-based adjuvants. These findings offer a transformative strategy for protecting aging populations against seasonal influenza and future pandemic."

Infectious Disease • Influenza • Respiratory Diseases

Chemically regulated STING-activating prodrugs of deoxyribose cyclic dinucleotides elicit robust immune activation and durable antitumor immunity (AACR 2026) - "In mice, all three prodrugs induced stronger systemic cytokine responses than ADU-S100 or the parent CDN 3′,3′-c-di-dAMP... Phosphotriester chirality is a critical determinant of dCDN prodrug activity. (Rp,Rp)-10 represents a promising next-generation STING agonist with potent systemic antitumor immunity and durable therapeutic effects. These findings underscore the importance of stereochemical control in the rational design of STING-targeted cancer immunotherapies."

Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • GLI2 • IFNB1 • STING

Activation of the cGAS-STING signaling pathway as an immunotherapeutic approach to glioblastoma (AACR 2026) - "Despite this variability, murine GBM cells consistently responded to exposure to STING agonist ADU-S100 with transient IRF3 phosphorylation and robust induction of type I interferons (IFN-β) and chemokines (CXCL10, CCL5)...Rechallenge of the same GBM cells in the contralateral hemisphere in long-term survivors was rejected, indicative of immune memory. These findings support pharmacological cGAS-STING activation as a strategy to counter GBM-driven immune suppression and a promising immunotherapeutic approach to this deadly brain tumor."

IO biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CGAS • CXCL10 • IFNB1 • TP53

STING agonist ADU-S100 in combination with vemurafenib induces STING upregulation, immune-stimulatory cytokine modulation and enhancing NK-mediated cytotoxicity in BRAF V600E-mutant melanoma (AACR 2025) - "The combination of STING agonist ADU-S100 and vemurafenib effectively enhances immune-stimulatory cytokine profiles in BRAF V600E-mutant melanoma. Notably, this approach may be used to promote NK cell-mediated cytotoxicity and modulation of key cytokines associated with immune resistance. This strategy shows promise for overcoming resistance and improving outcomes, warranting further clinical investigation."

Combination therapy • IO biomarker • Melanoma • Oncology • Solid Tumor • B2M • BRAF • CXCL13 • CXCL5 • CXCL8 • STING

Nano-Enabled Systemic Delivery of STING Agonist by Engineered Silicasome for Potent Antitumor Immunotherapy. (PubMed, Adv Sci (Weinh)) - "Here, we develop an engineered silicasome nanocarrier for systemic delivery of the CDN ADU-S100 (ADU-Sili)...Notably, combining ADU-Sili with immune checkpoint blockade (ICB) synergistically enhanced antitumor efficacy as demonstrated in more clinically relevant orthotopic tumor models. In summary, silicasomes enable effective systemic CDN delivery, eliciting robust immune and antitumor responses and overcoming intratumoral delivery limitations in STING-based cancer immunotherapy."

Journal • Oncology

Role of major facilitative folate transporters SLC19A1 and SLC46A1 in cyclic dinucleotide transport and STING signaling (AACR 2024) - "In R1-11/Tet-on-RFC cells, ADU-S100 showed a low affinity for binding to RFC, as measured by direct competition for transport with [3H]methotrexate...Maximum induction of pIRF3/IFNβ was seen in THP-1 and R1-11/Tet-on-RFC cells by ADU-S100 treatment at pH 7.2 (RFC pH optimum) in the presence of 25 nM leucovorin...In conclusion, RFC mediates ADU-S100 uptake and STING activation under physiologic conditions and this process is enhanced by concomitant expression of PCFT. Additional characterization of key molecular and biochemical determinants of CDN-based cancer therapeutics may lead to improved approaches for CDN therapy based on enhanced cellular uptake."

Oncology • IFNB1 • STING

STING agonist ADU-S100 improves the antitumor response of CLDN18.2/CD3 BiTEs by enhancing stem-like tumor-reactive CD8+ T cells in pancreatic adenocarcinoma (AACR 2024) - "By qPCR, western blot and flow cytometry, an orthotopic transplantation mouse model of pancreatic cancer and an in vitro tumor-PBMC coculture system were established to reveal the potential molecular mechanism of STING agonist ADU-S100 in optimizing the effects of CLDN18.2/CD3 BiTEs (IBI389). In PDAC organoids, IBI389 induced potent, specific cytotoxicity, the CLDN18.2 BiTEs significantly engaged human CD3+ T cells with tumor cells in an organoid-PBMC coculture system in vitro, resulting in the formation of the immunological synapse (IS). Pancreatic tumors appear to evade immune response by inducing immune-suppressive tumor microenvironment development. In mice, the combination of STING agonist ADU-S100 and CLDN18.2 BiTEs increased the proportion of memory and stem-like CD4+ and CD8+ T cells while decreasing the proportion of regulatory and exhausted T cells in pancreatic tumors, eradicating all detectable tumors. This data may be utilized to formulate immune-based..."

Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD8 • CLDN18 • HAVCR2 • IL2RA • IL7R • ISG20 • PD-1

Sting pathway activation potentiates the antitumor efficacy of doxorubicin in soft-tissue sarcoma (AACR 2025) - "STING pathway activation by ADU-S100 enhances the antitumor efficacy of doxorubicin in STS, suggesting that combining doxorubicin with ADU-S100 may be a promising strategy for future clinical trials."

Clinical • IO biomarker • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • PTPRC

Vaccination with an African Swine Fever Virus Multiepitope Protein Chitosan Nanoparticle-Based Subunit Vaccine Elicits Robust Immune Responses In Vivo. (PubMed, Vaccines (Basel)) - "These promising preliminary immunological findings suggest that this nanoparticle vaccine has the potential to confer protection against ASFV challenge, a hypothesis that will be examined in future studies."

Journal • Preclinical • Infectious Disease

Integrating STING Activation with Programmed Death-Ligand 1 Inhibition: Novel Approaches for Cancer Treatment. (PubMed, Crit Rev Oncol Hematol) - "In contrast, early-phase clinical trials of STING agonists, including ADU-S100, SYNB1891, IMSA101, and MK-1454, have shown acceptable safety and pathway engagement but generally modest and variable clinical responses, primarily reflected by low objective response rates and limited disease stabilization. We highlight emerging drug delivery platforms, such as nanocarriers, antibody-drug conjugates, and exosome-based systems, as key modulators of efficacy and safety, and emphasize the importance of biomarker-guided approaches for patient stratification and trial optimization. By integrating biological insight with translational feasibility, this review provides a framework for advancing STING-based combination immunotherapy toward more durable and personalized cancer treatment."

IO biomarker • Journal • Review • Oncology • PD-L1 • STING

Pharmacological STING Activation Enhances Autophagy-Mediated Clearance of Mycobacterium tuberculosis in Human Macrophages. (PubMed, J Innate Immun) - "Activating the STING pathway with ADU-S100 is a potent host-directed strategy to bolster macrophage autophagy and enhance the elimination of intracellular Mtb. This provides a strong rationale for exploring STING agonists as a novel therapeutic intervention for tuberculosis, addressing a significant and clinically relevant challenge in infectious disease."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • STING

A phase 2 study of STING agonist ADU-S100 combined with a CLDN18.2 bispecific antibody in patients with advanced pancreatic cancer. (ASCO-GI 2026) - "Combining the STING agonist ADU-S100 with a CLDN18.2 BsAb is feasible with a predictable safety profile. The regimen shows promising clinical activity and induces favorable immune changes in the tumor microenvironment of PDAC pts, supporting further development of this combination strategy."

Clinical • IO biomarker • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • CLDN18 • PD-1