ADU-S100 / Novartis - LARVOL DELTA

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

INTERFERON STIMULATED GENE SCORES ARE ELEVATED IN THE MYELOID COMPARTMENT OF MURINE KP UNDIFFERENTIATED PLEOMORPHIC TUMORS TREATED WITH TRANSLATIONAL STING AGONISTS (CTOS 2024) - "The objectives of the present study are; 1) To evaluate the anti-tumor potential of two clinically relevant STING agonists; ADU-S100 (CDN) and E7766, 2) To examine the importance of UPS cell STING expression for stimulating anti-tumor responses, and 3) To identify which populations in the UPS TME engage in STING signaling following therapy. To evaluate survival frequencies with translational STING agonists, immune competent C57Bl/6 mice were engrafted with 100,000 UPS cells and treated intratumorally with escalating doses of CDN or E7766 and followed over time using tumor volume measurements and bioluminescence imaging. We are thrilled to report that E7766 is a translational STING agonist capable of stimulating tumor clearance in the KP model of UPS. Additionally, we have established that tumor clearance phenotypes in this model are independent of UPS cell STING expression status. Moreover, neutrophils and myeloid cells in general appear to be important populations in..."

IO biomarker • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • STING

Intranasal immunization with CPAF combined with ADU-S100 induces an effector CD4 T cell response and reduces bacterial burden following intravaginal infection with Chlamydia muridarum. (PubMed, Vaccine) - "We determined that intranasal immunization with CPAF plus ADU-S100 was well tolerated in female mice, induced CD4 T cells characterized by TNFα production alone or in combination with IL-17 A or IFNγ, significantly reduced bacterial shedding, and shortened the duration of infection in mice intravaginally challenged with Chlamydia muridarum. These data demonstrate the potential for CDA as a mucosal adjuvant for vaccines against Chlamydia genital tract infection."

Journal • Infectious Disease • Vaginitis • CD4 • IFNG • IL17A • STING • TNFA

Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses. (PubMed, J Immunother Cancer) - "Our results suggest that STING agonists may be able to work indirectly in MCC via signaling through immune and stromal cells in the TME, and may not necessarily need STING expression in the cancer cells. This approach may be particularly effective in tumors that are already infiltrated by inflammatory cells in the TME but are evading immune detection via HLA-I downregulation."

Biomarker • IO biomarker • Journal • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • CD8 • STING

Intradermal vaccination with a phytoglycogen nanoparticle and STING agonist induces cytotoxic T lymphocyte-mediated antitumor immunity. (PubMed, NPJ Vaccines) - "This study evaluated whether combining a cationic plant-derived nanoparticle adjuvant (Nano-11) with the clinically tested STING agonist ADU-S100 (MIW815) could stimulate anticancer immunity by intradermal vaccination...Therapeutic vaccination with NanoST increased mouse survival by inhibiting B16-OVA tumor growth, and this effect was further enhanced by PD-1 checkpoint blockade. Our study provides a strong rationale for developing NanoST as an adjuvant for intradermal vaccination and next-generation preventative and therapeutic cancer vaccines by STING-targeted activation."

Journal • Hematological Malignancies • Lymphoma • Melanoma • Oncology • Solid Tumor • CD4 • CD8

Evaluation of Efficacy of Surface Coated versus Encapsulated Influenza Antigens in Mannose-Chitosan Nanoparticle-Based Intranasal Vaccine in Swine. (PubMed, Vaccines (Basel)) - "The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose-chitosan nanoparticles (mChit-NPs)...Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Improving STING agonist-based cancer therapy by inhibiting the autophagy-related protein VPS34. (PubMed, Oncoimmunology) - "We have recently demonstrated that inhibiting VPS34 enhances T-cell-recruiting chemokines through the activation of the cGAS/STING pathway using the STING agonist ADU-S100. Combining VPS34 inhibitors with ADU-S100 increased cytokine release and improved tumor control in mouse models, suggesting a potential synergy between VPS34 inhibition and therapies based on STING agonists."

Journal • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Characterization of a novel functional porcine CD3+CD4lowCD8α+CD8β+ T-helper/memory lymphocyte subset in the respiratory tract lymphoid tissues of swine influenza A virus vaccinated pigs. (PubMed, Vet Immunol Immunopathol) - "To understand the possible functional role/s of these cells, we characterized the antigen-specific T cell memory responses by multi-color flow cytometry in pigs vaccinated with a whole inactivated SwIAV vaccine, formulated with a phytoglycogen nanoparticle/STING agonist (ADU-S100) adjuvant (NanoS100-SwIAV)...These observations highlight the heterogeneity and plasticity of porcine CD4+ T-helper/memory cells in response to respiratory viral infection in pigs. Comprehensive systems immunology studies are needed to further decipher the cellular lineages and functional role/s of this porcine T helper/memory cell subset."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases • CD4 • IFNG • IL17A

PDE-stable 2'3'-cGAMP analogues, containing 5'-S-phosphorothioester linkage, as STING agonists. (PubMed, RSC Med Chem) - "An alternative phosphorothioate (referred to as endo-S-phosphorothioate) whereby the sulfur atom is endo to the cyclic phosphate ring (i.e. 5'-S-phosphorothioester linkage) would not have chirality at phosphorus and hence not pose diastereomer separation problems. Herein, we report the design and synthesis of novel 5'-endo-phosphorothioate substituted 2'3'cGAMP analogues that are hydrolytically stable towards both ectonucleotide phosphodiesterase I (ENPP1, a mammalian phosphodiesterase) and poxvirus immune nucleases (poxin, a phosphodiesterase in Poxvirus) but retains STING-TBK1-IRF activation, comparable to clinical candidate, ADU-S100 in THP1 monocytes."

Journal • Oncology • ENPP1 • GLI2 • STING

2',4'-LNA-Functionalized 5'-S-phosphorothioester CDNs as STING agonist. (PubMed, Chembiochem) - "Interestingly, some of our synthesized LNA 3'3'-endo-S-CDNs can moderately activate hSTING REF haplotype (R232H), which exhibit diminished response to both 2'3'-cGAMP and ADU-S100. Also, we show that one of our most potent endo-S-CDNs has remarkable chemical (oxidants I2 and H2O2) and phosphodiesterase stability."

Journal • Oncology • CGAS • GLI2 • 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

Mannose-chitosan nanoparticle surface adsorbed inactivated influenza virus vaccine elicits cross-protective humoral immunity in pigs (IMMUNOLOGY 2024) - "We developed whole inactivated SwIV H1N2 based mannose-chitosan nanoparticle (mChit-SwIV-NP) vaccine containing STING (stimulator of interferon gene) adjuvant ADU-S100, either both encapsulated (mChit-SwIV+S100-eNP) or surface adsorbed (mChit-SwIV+S100-sNP)...In summary, intranasal mChit-SwIV+S100-sNP vaccine elicited cross-reactive antibody while mChit-SwIV+S100-eNP vaccine induced mucosal and systemic cell-mediated immune responses higher than commercial SwIV vaccinates. Suggesting that mannose-chitosan nanoparticle vaccine has a promise in mitigating SwIV infections and transmission in swine herds."

Infectious Disease • Influenza • Respiratory Diseases • IFNG • IL17A • STING

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