ADU-S100 / Novartis - LARVOL DELTA

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

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 • 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 • Oncology • 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

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

Synergistic Activation of the STING Pathway via a Mn(II)-Cross-Linked Gel Scaffold To Boost Antitumor Immunotherapy. (PubMed, ACS Appl Mater Interfaces) - "In this work, a therapeutic gel scaffold made from Mn2+-cross-linked sodium alginate (Mn(II)-SA-Gel), which contains a stimulator of interferon genes (STING) agonist (ADU-S100) and an immune checkpoint inhibitor (aCTLA-4), was developed as a drug delivery system for cancer therapy...Moreover, Mn2+ promotes the generation of highly cytotoxic hydroxyl free radicals in the presence of H2O2, and in combination with the immune checkpoint inhibitor aCTLA-4, enhances the T-cell immune response to enhance their powerful tumor cell-killing effect. The findings indicated that Mn(II)-SA-Gel could serve as a promising platform to synergistically stimulate the STING pathway, thereby improving cancer immunotherapy."

Journal • Oncology • STING

cGAS-STING Pathway Activation Enhances Antitumor Effect of Talaporfin Photodynamic Therapy Through ROS Production. (PubMed, Cancer Sci) - "Furthermore, the efficacy of STING agonist (2'-3'-cyclic GMP-AMP sodium and ADU-S100) and TS-PDT combination was assessed in a xenograft tumor model. STING is an important regulator of cellular ROS homeostasis and tumor cell susceptibility to ROS in PDT. Combining a STING agonist with PDT could enhance its therapeutic efficacy and may have potential for future clinical applications."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Ce6 derivative photodynamic therapy triggers PANoptosis and enhances antitumor immunity with LAG3 blockade in cutaneous squamous cell carcinoma. (PubMed, Cell Rep Med) - "Incorporating lymphocyte activation gene 3 (LAG3) blockade further strengthens systemic antitumor immunity by suppressing myeloid-derived suppressor cells while augmenting type 2 conventional dendritic cells, cytotoxic T lymphocytes, and tissue-resident memory T cells. Our findings highlight the potential of STBF-PDT-STING agonism-anti-LAG3 combinations for metastatic and locally advanced cSCC."

Journal • Genetic Disorders • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • LAG3 • STING

LASIP: Light-Activated STING Immunotherapeutic Patch: A Multifunctional Microneedle Platform for Combinatorial Mild Hyperthermia with Immunotherapy in Breast Cancer. (PubMed, ACS Appl Mater Interfaces) - "LASIP is a transformative dissolvable microneedle patch loaded with antiPD-L1 antibodies, liposomal formulation of drugs (ADU-S100) that activate the stimulator of interferon genes (STING) pathway, and liposomal formulation of a biocompatible dye (IR783) that converts near-infrared light to mild hyperthermia (∼43 °C)...We show an "immunometabolic" correlation of these key metabolites to markers of DC maturation, Tregs, STING activation, and cytokines. Our findings demonstrate that by integrating three treatment modalities, LASIP elicits both innate and adaptive immune responses and enables metabolic reprogramming in the tumor microenvironment to enable antitumor immunity."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • STING

A Novel CPAF-STING Agonist Conjugate Vaccine Protects Female Mice Against Genital Chlamydia muridarum Infection (ASM Microbe 2025) - "We determined that intranasal immunization with the CPAF-CL1151 conjugate provided equivalent immunogenicity and protection, compared to an admixture with CPAF plus the STING agonist ADU-S100, despite the conjugate vaccine using 25-fold less agonist...Furthermore, the addition of the saponin Quil-A to CPAF-CL1151 delivered via intramuscular immunization significantly reduced bacterial burden and time to clearance. Future experiments will investigate the efficacy of other TLR/STING agonist conjugates and saponin liposomes with the goal of advancing the top candidate to human clinical trials."

Preclinical • Infectious Disease • Inflammation • CD4 • IFNG • IL17A • TNFA

IFNAR1 and IFNγ Are Necessary for Optimal Vaccine-Elicited Immune Protection Against Chlamydia muridarum Genital Infection and Disease Following Intranasal Immunization with Recombinant CPAF and a STING Agonist (ASM Microbe 2025) - "Intranasal administration of recombinant CPAF, in combination with the STING (STimulator of INterferon Genes) agonist ADU-S100 induced a protective CD4 T cell response in female mice characterized by production of TNF-α alone and in combination with IL-17A or IFN-γ...Vaccinated IFNAR1-deficient mice had similar levels of burden during challenge to vaccinated wild-type mice, but an increased frequency of hydrosalpinx, and enhanced mononuclear cell infiltrates. Future experiments will investigate the cellular mechanisms underlying the protective role of type-1 and type-2 interferons against chlamydial oviduct disease following vaccination."

Fallopian Tube Cancer • Gynecology • Infectious Disease • Infertility • Inflammation • Musculoskeletal Pain • Pain • Sexual Disorders • CD4 • IFNAR1 • IFNG • IL17A • IL1R1 • IL6 • STING • TNFA

Metabolic Regulation of cGAS-STING Signaling in the Tumor Microenvironment: Dual Immune Roles and Therapeutic Implications. (PubMed, Cytokine Growth Factor Rev) - "Current therapeutic strategies prioritize isoform-specific agonists (e.g. cyclic dinucleotides like ADU-S100; non-CDNs like diABZI) and precision delivery systems, such as nanoparticles and engineered bacteria, to address challenges like short half-life and systemic toxicity...However, the pathway's dual roles, particularly its tumor-promoting effects in advanced malignancies, necessitate context-dependent modulation. This review integrates preclinical insights and clinical trial data to outline strategies for harnessing cGAS-STING signaling in cancer immunotherapy while balancing its immunostimulatory and immunosuppressive outputs."

Biomarker • Journal • Review • Oncology • MIR25 • MIR93 • TLR4

STING-mediated neutrophil recruitment in DRG: A potential driver of alloknesis in atopic dermatitis (SID 2025) - "Moreover, intrathecal administration of the STING agonist ADU-S100 induced alloknesis and significantly increased neutrophil infiltration in the DRG, along with upregulation of NET-associated genes...These findings suggest that STING activation in DRG neurons drives neutrophil recruitment and activation, contributing to alloknesis in AD. Further research into neuro-neutrophil interactions in the DRG may provide new insights into itch sensitization in AD and serve as a potential therapeutic target for chronic itch."

Late-breaking abstract • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CTSG • IL6 • STING

Cutaneous STING pathway agonism enhances the immunogenicity of a SARS-CoV-2 ferritin nanoparticle vaccine in both young and aged mice (SID 2025) - "Notably, the key immunopotentiating benefits of ADU-S100 as a skin adjuvant is evident in both young and aged mice, as well as in translational studies using human skin models. Together, SpFN+ADU-S100 MNP supports the utility of emerging bioengineering platforms and adjuvants for the development of a next-generation coronavirus vaccine focused on addressing the limitations of authorized SARS-CoV-2 vaccines."

Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CCL2 • CXCL10 • IFNB1

Unleashing anti-tumor immunity: Targeting the autophagy-related protein VPS34 to enhance STING agonist-based therapy. (PubMed, Autophagy Rep) - "In vivo, treatment with the VPS34 inhibitor SB02024 enhances the positive effects of the STING agonist ADU-S100 in melanoma tumor-bearing mice. Thus, our study suggests that VPS34 inhibitors could be used to enhance STING-based anticancer therapies. CCL5 (C-C motif chemokine 5); CXCL10 (C-X-C motif chemokine 10); IFN (interferon); VPS34 (vacuolar protein sorting 34); cGAS (cyclic GMP-AMP Synthase); STING (stimulator of interferon genes protein); cGAMP (2'3'-cyclic guanosine monophosphate-adenosine monophosphate)."

IO biomarker • Journal • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CCL5 • CGAS • CXCL10 • IFNB1 • STING

Intravenous delivery of STING agonists using acid-sensitive polycationic polymer-modified lipid nanoparticles for enhanced tumor immunotherapy. (PubMed, Acta Pharm Sin B) - "In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • STING

pH-responsive nano-vaccine combined with anti-PD-1 antibodies for enhanced immunotherapy of breast cancer. (PubMed, Theranostics) - " A pH-responsive amphiphilic diblock copolymer was synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization and conjugated with STING agonist ADU-S100 and mannose to specifically target dendritic cells (DCs)...The combination with anti-PD-1 antibodies further enhanced tumor control, immune cell infiltration, and survival rates compared to monotherapy. The pH-responsive nano-vaccine combined with anti-PD-1 antibodies showed remarkable synergistic effects in BC treatment, highlighting its potential to enhance immune checkpoint blockade therapy and offer a promising strategy for clinical applications in solid tumors."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • CD80 • CD86

ELF4 improves sepsis-induced myocardial injury by regulating STING signaling-mediated T cells differentiation. (PubMed, Cell Biol Toxicol) - "The mice were injected intraperitoneally with STING agonist ADU-S100 and C-176 after modeling...Furthermore, ELF4 was found to inhibit STING activation, reducing T cells differentiation into pro-inflammatory subsets. Overexpression of ELF4 in CD4+ T cells ameliorated myocardial damage and improved cardiac function in CLP mice, suggesting that the ELF4-STING signaling axis plays a protective role in sepsis-induced myocardial injury by regulating T cells differentiation."

Journal • Cardiomyopathy • Cardiovascular • Infectious Disease • Inflammation • Septic Shock • CD4

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

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

The combination of a STING agonist and IL15 efficiently reverses the immunosuppressive tumor microenvironment in a complex primary human organoid model (ITOC 2025) - "Upon treatment with IL-15, a STING agonist (ADU-S100) or a combination of both for 48 hours immune cell responses and tumor cell death were analyzed by flow cytometry...Tumor cell killing in response to STING pathway stimulation and combination treatment was partially dependent on cell-cell contact as spatial separation of NK cells resulted in a significantly reduced degranulation and tumor cell death. Conclusions Combination treatment of a STING agonist and IL-15 modulates the microenvironment into a pro-inflammatory state and synergistically supports immune cell-mediated tumor cell killing in a TME mimicking 3D model of tumor organoids, CAFs and innate immune cells."

Biomarker • Tumor microenvironment • Colorectal Cancer • Oncology • Solid Tumor • CAFs • IL15 • STING • TNFA