ADU-S100 / Novartis - LARVOL DELTA

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

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

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

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

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

STING agonist-loaded cationic radioactive microspheres enhance transarterial radioembolization of hepatocellular carcinoma via tumor immune activation. (PubMed, Mater Horiz) - "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."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD8

Activation of the STING pathway potentiates the antitumor efficacy of doxorubicin in soft-tissue sarcoma. (PubMed, Front Oncol) - "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."

Journal • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • PTPRC

Photodynamic immunotherapy using adu-S100-modified nanoparticles combined with icb to treat triple-negative breast cancer (ASH 2025) - "In general, this NP system will have many applications in cancer treatment. ( Acknowledgements: This study was supported by Grant from School of Public Health of Southern Medical University, China, Grant No.GW202431; Corresponding author: Hong Cao, gzhcao@smu.edu.cn )."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • CXCL10

Role of adjuvants in the efficacy of an IZUMO1-based immunocontraceptive vaccine in mice. (PubMed, Vaccine) - "The adjuvants were AddaS03, the nanoparticle adjuvant NanoST, composed of α-D-glucan nanoparticles and the STING agonist ADU-S100, or a combination of these two adjuvants...Infertility correlated with IgG directed against epitopes in the hairpin region of IZUMO1. These results support the further development of IZUMO1-based immunocontraceptive vaccines for wildlife population control."

Journal • Preclinical • Infertility • Sexual Disorders

Investigating innate immune targeting of pediatric high grade glioma via STING immunostimulation and therapeutic anti-tumor antibodies (SNO 2025) - "We demonstrate that STING pathway components are expressed in pHGG cells and that treatment with the STING agonist ADU-S100 induces robust downstream signaling, resulting in type I interferon secretion and increased cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays...Delivery of the anti-GD2 monoclonal antibody Dinutuximab to these tumors activates the anti-tumor effects of PBMCs. Lastly, we explore tumor modulation of the GD2 target when undergoing immune stress. These findings highlight promising therapeutic approaches for pHGG, emphasizing the potential of targeted immunotherapies and increasing our understanding of tumor response to immune pressure."

Clinical • IO biomarker • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • STING

Characterization of the cGAS-STING pathway as a novel approach to targeting glioblastoma (SNO 2025) - "Lastly, we have recently shown that the combination of the STING agonist ADU-S100 and the MEK inhibitor Trametinib produces synergy through enhanced secretion of CXCL10 and increased phosphorylation of STAT1. This novel discovery may inform future combination treatment approaches and studies to validate this finding in vivo, using GBM preclinical mouse models, are currently underway."

Brain Cancer • Glioblastoma • Solid Tumor • CXCL10

Leveraging the cGAS-STING pathway to modulate the tumor microenvironment and enhance immunotherapies in glioblastoma (SNO 2025) - "STING was activated using synthetic agonists (e.g., ADU-S100), alone or in combination with autophagy inhibitors or G47Δ oncolytic herpes simplex virus (oHSV) therapy... Our data highlight the therapeutic promise of cGAS-STING modulation in GBM. While oHSV therapy may antagonize STING signaling, combining STING activation with autophagy inhibition can potentiate innate immune responses. Ongoing in vivo studies aim to define how these therapies reshape the TME and improve treatment efficacy."

Biomarker • IO biomarker • Tumor microenvironment • Brain Cancer • Glioblastoma • Herpes Simplex • Oncology • Solid Tumor • CXCL10 • IFNB1

Investigating innate immune targeting of pediatric high grade glioma via STING immunostimulation and therapeutic anti-tumor antibodies (WFNOS 2025) - "We demonstrate that STING pathway components are expressed in pHGG cells and that treatment with the STING agonist ADU-S100 induces robust downstream signaling, resulting in type I interferon secretion and increased cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays...Delivery of the anti-GD2 monoclonal antibody Dinutuximab to these tumors activates the anti-tumor effects of PBMCs. Lastly, we explore tumor modulation of the GD2 target when undergoing immune stress. These findings highlight promising therapeutic approaches for pHGG, emphasizing the potential of targeted immunotherapies and increasing our understanding of tumor response to immune pressure."

Clinical • IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • STING

Leveraging the cGAS-STING pathway to modulate the tumor microenvironment and enhance immunotherapies in glioblastoma (WFNOS 2025) - "STING was activated using synthetic agonists (e.g., ADU-S100), alone or in combination with autophagy inhibitors or G47Δ oncolytic herpes simplex virus (oHSV) therapy... Our data highlight the therapeutic promise of cGAS-STING modulation in GBM. While oHSV therapy may antagonize STING signaling, combining STING activation with autophagy inhibition can potentiate innate immune responses. Ongoing in vivo studies aim to define how these therapies reshape the TME and improve treatment efficacy."

Biomarker • IO biomarker • Tumor microenvironment • Brain Cancer • Glioblastoma • Herpes Simplex • Solid Tumor • CXCL10 • IFNB1

Characterization of the cGAS-STING pathway as a novel approach to targeting glioblastoma (WFNOS 2025) - "Lastly, we have recently shown that the combination of the STING agonist ADU-S100 and the MEK inhibitor Trametinib produces synergy through enhanced secretion of CXCL10 and increased phosphorylation of STAT1. This novel discovery may inform future combination treatment approaches and studies to validate this finding in vivo, using GBM preclinical mouse models, are currently underway."

Brain Cancer • Glioblastoma • Solid Tumor • CXCL10

Targeting the cGAS-STING Pathway for Cancer Immunotherapy: From Small-Molecule Agonists to Advanced Nanomaterials. (PubMed, Mol Pharm) - "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."

IO biomarker • Journal • Review • Oncology • CGAS • STING

Intratumoral B cells are essential for anti-tumor immune responses of tertiary lymphoid structures: Impact of STING and LTβR activation in pancreatic cancer (SITC 2025) - "Tumors were treated with STING agonist ADU-S100 and anti-LTβR antibody...This approach offers a promising immunotherapy strategy for immune-cold tumors resistant to conventional treatments.Abstract 882 Figure 1Request permissionsSTING+LTβR therapy induces intratumoral B cell-rich TLS and HEVs in pancreatic tumors, enhancing antitumor immunity and survival, and supporting TLS-derived IgG binding to KPC tumor cellsAbstract 882 Figure 2Request permissionsSTING+LTβR therapy expands intratumoral B cell subsets and Ig isotypes. TLS-derived hybridoma antibodies bind KPC tumor cells, and hybridoma IgG clones show tumor specificity, supporting humoral contributions to antitumor immunity"

Hematological Malignancies • Multiple Myeloma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD79A • STING

Understanding STING signaling in glioblastoma; Identifying a role for STING in tumor cells (SITC 2025) - "Our Lab previously showed that a small molecule STING agonist (ADU-S100), can turn on the pathway and improve survival in mouse GBM models...Our data shows that GBM cells can respond to STING agonists, suggesting additional functions of STING signaling which may facilitate tumor growth. These are currently under investigation."

Tumor cell • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • STING

Melanoma cell–intrinsic regulation of tertiary lymphoid structure formation by STING signaling (SITC 2025) - "Using Yumm1.7 mouse melanoma models in STING-deficient hosts, we evaluated TLS formation following STING agonist ADU-S100 and 5-aza-2'-deoxycytidine (5AZADC) treatment by immunohistochemistry and multiplex immunofluorescence.Results We identified a strong correlation between STING-expressing tumors and each of the twelve chemokines in melanoma samples, particularly with secondary lymphoid organ-associated chemokines CCL19 (r = 0.61), CCL21 (r = 0.42), and CXCL13 (r = 0.60)...This work was funded by the NCI-NIH (P30 CA076292, and P50 CA168536), CJG Fund, Chris Sullivan Fund, V Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Melanoma Research Foundation (MRF) Career Development Award, and Moffitt Cancer Center Melanoma and Skin Cancer Center of Excellence Award."

IO biomarker • Colorectal Cancer • Melanoma • Oncology • Solid Tumor • CCL19 • CCL21 • CXCL10 • CXCL13

Reprogramming The Tumor Immune Microenvironment: STING activation synergies with BRAF inhibition to boost NK-mediated Cytotoxicity in BRAF V600E Mutant Melanoma (SITC 2025) - "We hypothesized that combining the STING agonist ADU-S100 with the BRAFi vemurafenib would synergistically augment NK cell cytotoxicity and promote a more immunogenic TME.Methods Three human BRAF V600E mutant melanoma cell lines (SKMEL24, HTB66, SH4) were treated with vehicle, ADU-S100, vemurafenib, or the combination. IL8: key cytokine in melanoma metastasis level decreased in combination group significantly when compared to control. VEGF level reduction compared to control observed across all cell lines the favorable change in CXCL13/CXCL5 (increase/decrease) which is associated with melanoma progression and responsiveness to targeted immune therapy was observed across all cell line when compared to base levels"

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

Light Metabolically Reprograms CD8+ T Cells to Potentiate STING-Driven Tumor Eradication and Prevent Metastasis. (PubMed, Adv Sci (Weinh)) - "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."

IO biomarker • Journal • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • CD8 • STING