Sting agonist clinical trial. Jan 16, 2025 · ABSTRACT.

Sting agonist clinical trial Activation of STING with a specific agonist, as a monotherapy or in combination with anti-PD1 therapy, may be a promising novel anticancer strategy. Recent Findings Preclinical data has shown that the addition of a STING agonist enhances the effect of current treatments such as Mar 30, 2022 · ADU-S100 (MIW815)—a synthetic CDN that mimics an endogenous cyclic dinucleotide called cGAMP is the native substrate of human STING and activates all known variants of human STING—was the first STING agonist to be evaluated as a cancer immunotherapy in clinical trials. Patients and Methods:. A STING agonist antibody–drug conjugate (ADC) could overcome current limitations by improving tumor accessibility, allowing for systemic administration as well as tumor-localized activation of STING for greater anti-tumor activity and better such as immune checkpoint inhibitor antibodies and radiation therapy. delivery, which poses two main problems. The conjugation of STING agonists with polymer nanoparticles is shown to enhance stability, circulation time and BI 1703880 may selectively activate the STING pathway, resulting in dose-dependent local tumor control and the induction of a tumor-specific immune response 1. The available STING agonists are modified cyclic nucleotides that are delivered intratumorally and have achieved durable regressions in tumor models. study also showed that SHR1032 effectively promoted IFN-β production and potent anti-tumor properties in the MC38 murine syngeneic tumor model when administered intra-tumorally. - These proinflammatory cytokines aim to activate dendritic cells, macrophages, and natural killer cells, and subsequently mobilize adaptive immune cells against tumor cells Oct 16, 2018 · Stimulation of STING should be transient, not chronic, and use of STING agonists is limited to intratumoral injections, similar to TLR9, in order to avoid potentially severe systemic effects. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. All STING agonists have an issue with off-target activity if they are administrated systematically [113, 114]. Sep 6, 2022 · Here, we have investigated an alternative approach to improving efficacy in BRCA-associated BC by combining PARP inhibition with STING agonism. But MK-1454 failed to produce any responses on its own in patients with advanced solid tumors or lymphomas in a phase 1 trial. Targeting the cGAS-STING pathway holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective tumor elimination. Front. Summary STING agonists are a new class of agents that activate the immune response to improve tumor control. These results are shaping the design of combination clinical trials in cancer patients. doi: 10. Sep 6, 2023 · Repeated failures of various attempts at hitting the Sting pathway have not deterred further work. It is a CDN analogue of the endogenous agonist 2′,3′-cGAMP containing 2′-3′- and 3′-5′-thiophosphodiester linkages on the c-di-AMP scaffold. Such STING agonists are being tested in clinical trials with the rationale of activating STING in tumor cells or tumor-infiltrating Jul 13, 2023 · STING agonists are often limited by low circulation time and cellular uptake. The initial STING agonist to enter clinical development was ADU-S100/MIW815 with first results reported at the Society for ImmunoTherapy of Cancer meeting in 2018 . This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody against PD-1, in 106 patients with advanced solid tumors or lymphomas. Here, we present initial data, including safety, efficacy, pharmacokinetics, and pharmacodynamics, for BI 1703880 plus ezabenlimab (anti-PD-1 antibody 1. Here we demonstrate that 2′3′-c-di-AM(PS) 2 (Rp,Rp), a STING agonist that has been undergoing clinical trials for antitumor immunotherapy, activates the STING signalosome in differentiating human T H 17 cells. TAK-676 is a synthetic Dec 1, 2023 · In fact, delivery systems for STING agonists, such as liposomal formulations and PLGA micro/nanoparticles, have already been developed and utilized [[36], [37], [38]]. 15:1342647. Mar 13, 2024 · This was in contrast to the group that received ADU-S100, a STING agonist used in clinical trials (Supplementary Fig. Nov 1, 2023 · In this line, STING was found to limit murine T H 17 pro-inflammatory program in vitro. Trials to determine optimal drug combinations and novel delivery mechanisms are continuing in development. May 10, 2024 · Here the authors report the characterization of the STING agonist IMSA101, showing that STING-induced IL18 secretion enhances CAR-T activity in preclinical cancer models. There was TAK-500 is a first-in-class STING agonist immunostimulatory antibody drug conjugate (iADC) that delivers dazostinag to CCR2+ myeloid cells in the tumor microenvironment Mechanism of Action 1,3-4 - By targeting the STING pathway and CCR2 expressing myeloid cells, TAK-500 may offer enhanced potency via improved PK and selective delivery. In this study, the mechanism of action of PTT and its connection to pyroptosis as well as the therapeutic potential of PTT alone and in combination with STING agonists, were investigated. BI 1703880 + ezabenlimab (PD-1 inhibitor) Jul 11, 2024 · Activation of the STING pathway can promote anti-tumor immunity. Feb 15, 2022 · AbstractPurpose:. Sep 16, 2024 · Several STING agonists have entered clinical trials, with many showing promising results in enhancing the efficacy of existing immunotherapies, such as immune checkpoint inhibitors . DOI: 10. Combining STING agonists with venetoclax represents a highly promising and novel therapeutic approach for AML and should be considered for accelerated early phase clinical trials. 1 In preclinical studies using a variety of murine tumor models Sep 4, 2023 · It is well-known that current STING agonists are mainly administered by intratumoral or intravenous routes, including ADU-S100, 30 MK1454, 13 GSK-3, 18 SR717, 20 HB3089, 21 and only a few can be administered orally like MSA-2 19 and BSP16. This study shows the potential clinical relevance of the use of combination STING Jan 27, 2023 · Purpose of Review New therapies are needed to potentiate the effects of current immunotherapies and overcome resistance. Jun 17, 2024 · STING agonist 8803 demonstrates synergy with anti–PD-1. When dosed intratumorally, SHR1032 induced strong anti-tumor effects in the MC38 murine syngeneic tumor model. Several agonists and inhibitors of the cGAS-STING pathway have been developed and evaluated for the treatment of various diseases. All trials on the list are NCI-supported clinical trials, which are sponsored or otherwise financially supported by NCI. Jun 2, 2022 · TAK-500 is a novel ISAC comprising a STING agonist (based on TAK-676, which is currently in phase 1 clinical trials [NCT04420884, NCT04879849]), an IgG1 anti-cysteine-cysteine chemokine receptor 2 (CCR2) antibody, and a self-immolating maleimide-containing protease-cleavable peptide linker. NCI’s basic information about clinical trials explains the types and phases of trials and how they are carried out. 42. 16_suppl. The STING agonists currently being tested in trials are ADU-S100/MIW815 and MK-1454, but additional molecules are advancing toward clinical development. MSA-2 is an oral non-nucleotide STING agonist, resolving the delivery flaw of conventional STING agonists . JCO 42 , TPS2690-TPS2690 (2024). injections of MIW815, 50 to 6,400 μg, on a 3-weeks-on/1-week-off schedule Jul 24, 2023 · While STING agonists have proven to be effective preclinically as anti-tumor agents, these promising results have yet to be translated in the clinic. Oct 16, 2020 · The fifth issue involves the route of administration of STING agonists as most agonists currently in clinical trials are largely focussed on i. Intratumoral injection of ALG-031048 in mice bearing CT26 tumor cells resulted in tumor regression in 90% of mice (compared to 44% with ADU-S100). The stimulator of IFN genes (STING) is a transmembrane protein that plays a role in the immune response to tumors. Jan 4, 2023 · Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. The STING agonist in combination with ezabenlimab is currently being evaluated in a Phase 1 clinical trial for the treatment of patients with advanced solid tumors 3. Background Anti-tumor efficacy of immuno-oncology (IO) approaches remains limited to a minority of tumor subtypes and considerable efforts remain focused on strategies to improve IO activity in immune-refractory or ‘cold’ tumors. Jun 16, 2020 · Such STING agonists are being tested in clinical trials with the rationale of activating STING in tumor cells or tumor-infiltrating immune cells (including dendritic cells) to elicit immunostimulatory effects, alone or in combination with a range of established chemotherapeutic and immunotherapeutic regimens. The cGAS-STING pathway is crucial for immune defense against pathogens and cancer, making STING a promising target for cancer immunotherapy. Citation: Li T, Zhang W, Niu M, Wu Y, Deng X and Zhou J (2024) STING agonist inflames the cervical cancer immune microenvironment and overcomes anti-PD-1 therapy resistance. coli Nissle Strain Expressing STING Agonist, with and without Atezolizumab in Advanced Malignancies Clin Cancer Res . Technical challenges such as clinical administration should be overcome in order to make STING agonists more widely used in clinical treatment. ONM-501 is comprised of a STING-activating pH-sensitive PC7A polymer conjugated with cGAMP. 1. The study was a phase I, single-arm dose-escalation study Mechanism of Action 1-5 - Dazostinag is a systemic STING agonist, leading to production of type I interferons and proinflammatory cytokines. The discussion concludes with an examination of the challenges facing the advancement of promising STING agonists in clinical trials and the pressing issues within the cGAS-STING signaling pathway research. Clinical trials look at new ways to Such STING agonists are being tested in clinical trials with the rationale of activating STING in tumor cells or tumor-infiltrating immune cells (including dendritic cells) to elicit immunostimulatory effects, alone or in combination with a range of established chemotherapeutic and immunotherapeutic regimens. News release. Suboptimal potency for human STING agonists and STING Agonists in Clinical Trials Flavonoid small molecule: dimethylxanthone acetic acid (DMXAA, ASA404, vadimezan) DMXAA was the first STING-targeted therapy to be evaluated in oncologic clinical trials and is the only agent to have reached Phase III . Mar 13, 2023 · A wide range of preclinical experiments, translational data, and ongoing clinical trials support the therapeutic use of STING agonists in patients. A myriad of pre-clinical studies have implicated the cGAS/stimulator of int … Mar 29, 2022 · The early hopes to learn from STING agonists, which have reached the clinics in recent years for selected oncology indications, have not yet materialized since the initial trials are progressing very slowly. Various new STING agonists, including BMS-986301 (NCT03956680) and BI 1,387,446 (NCT04147234), are currently evaluated in clinical trials either alone or May 29, 2024 · Cyclic dinucleotides (CDNs) such as cGAMP, the endogenous STING agonist, are not ideal clinical candidates for exogenous routes of delivery. Cell type-specific cGAMP transporters, hydrolases, and regulators together tightly regulate the paracrine cGAMP-STING signaling that can be harnessed to activate our powerful anti-cancer immune system. Additionally, uniSTING treatment decreased the frequency of CD62L + CD44 May 30, 2021 · The interrogation of intrinsic and adaptive resistance to cancer immunotherapy has identified lack of antigen presentation and type I interferon signaling as biomarkers of non-T-cell-inflamed tumors and clinical progression. Early trials showed limited efficacy with CDNs due to rapid clearance, degradation and/or off-target toxicity. The STING agonists, DMXAA and cGAMP, greatly enhanced CAR-T cell persistence in the tumor microenvironment [ 13 ]. The people in this study have sarcoma or MCC that has spread. Jan 27, 2023 · Preclinical data has shown that the addition of a STING agonist enhances the effect of current treatments such as immune checkpoint inhibitor antibodies and radiation therapy. Oct 8, 2022 · However, the delivery of conventional STING agonists depends on intratumoral injection, limiting their application in the clinic [28, 29]. 2024. Furthermore Jun 30, 2024 · The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is pivotal in immunotherapy. Full Title A Phase I Trial of CRD3874-SI, a STING Agonist, in Patients With Advanced/Metastatic Malignant Solid Tumors Purpose Researchers want to find the best dose of CRD3874-SI to use in people with sarcoma or Merkel cell carcinoma (MCC). One of Jan 16, 2024 · However, despite promising results in animal models, the first STING agonist to enter clinical trials, DMXAA (vadimezan), demonstrated poor efficacy against solid tumors either alone or in combination with chemotherapy . Correction: Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas. from publication: Challenges and Opportunities in the Clinical Development of STING Agonists for Cancer Immunotherapy | Immune Aug 20, 2020 · Merck already has a STING agonist in development, MK-1454. However, systemic administration of current STING In addition, chronic activation of the STING pathway has been found to be involved in autoimmune diseases as IFN overproduction. Prior receipt of therapeutic radiotherapy to all progressive lesions intended for PULSAR treatment. CCR-23-0118. This phase I study assessed the safety, pharmacokinetics (PKs), and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates the stimulator of IFN genes (STING) pathway, in patients with advanced/metastatic cancers. Dec 1, 2020 · Currently, clinical trials of STING agonists have focused on intradermal administration. The reasons for this are multifaceted but include major Feb 1, 2023 · From the limited clinical data of CDN-based STING agonists, combination with PD-1/PD-L1 presented a slight efficacy advantage concerning specific cancer types compared with STING agonist monotherapy [13], [14], [23], and a combination with checkpoint inhibitors is involved in most of all of the current clinical trials of STING agonists The early hopes to learn from STING agonists, which have reached the clinics in recent years for selected oncology indications, have not yet materialized since the initial trials are progressing very slowly. Results from the use of MK-1454 were initially reported at the European Society of Medical Oncology Meeting in 2018 (NCT03010176). • BI 1387446 is a STING agonist, administered IT, which in animal models has led to shrinkage and complete disappearance of injected and non-injected tumors, and durable anti-tumor memory. From the limited clinical data of CDN-based STING agonists, combination with PD-1/PD-L1 presented a slight efficacy advantage concerning specific cancer types compared with STING agonist monotherapy , , , and a combination with checkpoint inhibitors is involved in most of all of the current clinical trials of STING agonists. Aug 21, 2020 · Thus, CDN-based STING agonists currently undergoing clinical trials are dosed by direct intratumor injection, which limits their application to a narrow set of tumors. Anti-cancer therapy, except pembrolizumab and nivolumab, within 4 weeks or < 5 half-lives of the first dose of study treatment. Jan 12, 2021 · The combination of CDN-based STING agonists and ICIs demonstrated its therapeutic potentials in preclinical models, while the administration of STING agonists was only limited to intratumoral Jan 7, 2024 · The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing a crucial role in improving antitumor immunity through immune effector responses. Since a STING agonist would stimulate a proinflammatory response, the modulation of the PD-1 pathway may further potentiate the therapeutic effect of STING. This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody Download scientific diagram | STING Agonists in Clinical Trials. In 2008, DMXAA was used as a STING agonist in clinical trial treating refractory tumors (DART). The stimulator of interferon genes genes (STING) pathway is an innate immune activating cascade that may enhance current cancer immunotherapies. Here we report the first-in-human results for the STING agonist BI 1387446 alone (Arm A) and in combination with ezabenlimab (Arm B). As STING activation can upregulate programmed death ligand 1 and human leukocyte antigen in tumor cells, a combination of BI 1703880 and an anti-programmed cell death protein 1-antibody, such as ezabenlimab, may improve efficacy. Thus, research and development of STING agonists and inhibitors has been a hot field for the treatment of several diseases. Oct 2, 2024 · This scholarly review examines the diverse categories of STING agonists, encompassing CDN analogues, non-CDN chemotypes, CDN-infused exosomes, engineered bacterial vectors, and hybrid structures of small molecules-nucleic acids. 1158/1078-0432. A myriad of pre-clinical studies have implicated the cGAS/stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that drives activation of type I generated molecules that directly activate STING for use in oncological indications. Adjuvant is an essential component in subunit vaccines. Song et al. The past several years, especially 2018, has seen increasingly rapid advances in this field. I. 4,5 Phase I, first-in-human trial evaluating the STING agonist BI 1387446 alone and in combination with ezabenlimab in solid tumors #1030P Limited results are available from clinical trials using other STING agonists. 1342647 May 16, 2024 · Li recounts the characterization of the second messenger cGAMP as a key intercellular innate immune transmitter and development of its pharmacological analogs. In addition, a biomarker of PC was Nevertheless, there has been progress in identifying novel compounds, showing in some cases unexpected mode of action, that might move to early clinical trials in the very near future. May 1, 2023 · The first generation of STING agonists has been evaluated in clinical trials, including ADU-S100 and MK-1454. These developments highlight the potential of STING agonists to overcome resistance to conventional therapies and to improve outcomes in patients with various Feb 15, 2022 · Clinical Trial. Mar 12, 2024 · However, DMXAA, a preclinical STING agonist, failed to benefit cancer therapy in a phase III clinical trial due to its selective activation of murine STING, but not human STING. Nov 1, 2023 · GSK revealed the STING agonist cull in its third-quarter earnings (PDF) presentation, where the company also disclosed that two other candidates have been removed from its phase 1 pipeline. BI 1703880 is a novel, systemically administered, next-generation STING agonist with proven antitumor activity in vivo. Immunol. ALG-031048 is a novel STING agonist that has shown higher stability in in vitro studies compared to natural STING ligand and STING agonist ADU-S100. A wide May 15, 2024 · Furthermore, we delve into the latest clinical research on STING agonists and their potential in combination therapies, targeting this pathway. STING activation is an immunostimulatory approach, which may enhance the activity of standard therapies and improve efficacy. To address a broad spectrum of cancers, STING agonists that are suitable for systemic administration and preferentially target tumors are needed. 10e). Tumor targeted delivery of STING agonist Potent target-dependent anti-tumor activity in tumor models Improved efficacy and reduced systemic cytokines compared to a systemically administered diABZI STING agonist2 in mice Well-tolerated in repeat dose toxicology studies in NHP A Phase I clinical trial was initiated in January 2023 However, these STING agonists are either in infancy with limited biological effects or have failed in clinical trials. 1200/JCO. New therapies that activate an innate immune response and relieve this suppression may be beneficial to overcome this hurdle. Oct 20, 2018 · Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentation of preliminary data from a Phase 1 clinical trial evaluating MK-1454, an investigational STING (stimulator of interferon genes) agonist, as monotherapy and in combination with KEYTRUDA ® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with advanced solid tumors or lymphomas Mar 4, 2019 · Aduro’s STING agonist, ADU-S100, achieved a 5% response rate, which, he says, represents “meaningful clinical activity,” particularly as the drug raised proinflammatory cytokine production Oct 16, 2020 · In this review, we summarise the body of evidence supporting a synergistic role of STING agonists with currently approved ICI therapies and discuss whether, despite the numerous obstacles encountered to date, the clinical development of STING agonist as novel anti-cancer therapeutics may still hold the promise of broadening the reach of cancer Jan 4, 2023 · AbstractPurpose:. Jun 11, 2024 · The failure of the STING agonist DMXAA in clinical trials and the modest effects of ADU-S100 highlight the need for developing a new generation of drugs and improving their delivery methods. MSA-2 is a milestone in cancer immunotherapy, providing a promising adjuvant suitable for systemic . Nov 14, 2021 · Among them, the clinical trial of oral CXA-10 in the treatment of primary focal segmental glomerulosclerosis has entered phase 2, but no clinical trial of CXA-10 as a STING inhibitor in the treatment of related immune diseases has been reported. t. Early phase trials have demonstrated modest efficacy of STING agonists and revealed new mechanistic and technical challenges … Phase I trial of CRD3874-SI, a systemically administered STING agonist, in patients with advanced solid tumors. By utilizing the nanoprecipitation method, STING agonists were encapsulated into the hydrophobic core of micro/nanoparticles and thus effectively prevent its direct contact or interaction with the physiological environment, and STING agonist (BI 1703880) clinical trial. Recently discovered cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has … Jul 5, 2023 · Phase I Study of SYNB1891, an Engineered E. Dec 1, 2020 · This compound is the earliest STING agonist that enters in human clinical trial developed by Aduro Biotech as stimulatory immunotherapy for cancers. BI 1703880, a novel STimulator of INterferon Genes (STING) agonist, has demonstrated preclinical antitumor activity. May 20, 2022 · Compared to the clinical CDN STING agonist ADU-S100, SHR1032 has much higher activity in human cells with different STING haplotypes and robustly induces interferon β (IFNβ) production. Here the authors generate tumor cell-directed STING agonist antibody-drug conjugates that activate STING in tumor and myeloid cells Nov 2, 2023 · The combination of venetoclax and STING agonist shows marked efficacy in ex vivo and in vivo studies, including in models of TP53 defective AML. Many agonists of pathogen recognition receptors have been developed as potent adjuvants to optimize the immunogenicity and efficacy of vaccines. CRD3874-SI attaches to a type of protein called a STING. May 20, 2022 · Despite remarkable efficacy in many pre-clinical studies, only modest effects have been reported from clinical trials of CDN STING agonists 7,8. Mar 22, 2023 · STING agonists have shown limited efficacy in early-phase clinical trials despite promising pre-clinical data. The clinical trials on this list are studying sting agonist crd3874. Jun 16, 2020 · Such STING agonists are being tested in clinical trials with the rationale of activating STING in tumor cells or tumor-infiltrating immune cells (including dendritic cells) to elicit immunostimulatory effects, alone or in combination with a range of established chemotherapeutic and immunotherapeutic regimens. Boehringer Oct 15, 2021 · The clinical trial was initially designed to obtain a biopsy to confirm the pathologic diagnosis prior to administration of the STING agonist. Prior receipt of stimulator of interferon genes (STING) agonist. XMT-2056 delivers its STING agonist payload into HER2 + tumor cells and FcγRI (CD64)-expressing myeloid cells and activated STING signaling in both Apr 13, 2024 · Recently, STING agonists have appeared in clinical trials related to immunotherapy . A recently discovered innate immunity pathway, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), plays a critical role in anti-tumor immunity Mar 25, 2024 · While many STING agonists yield remarkable outcomes in mice, clinical trials have, unfortunately, yielded disappointing results thus far 4. The fifth issue involves the route of administration of STING agonists as most agonists currently in clinical trials are largely focussed on i. Just last week saw the planned entry into first-in-human studies of two Sting agonists: CuraDev’s CRD3874, and ONM-501, a “dual activating” project in development by the private US biotech OncoNano Medicine. Both are cyclic dinucleotide (CDN)-based compounds and are injected directly into tumors. Early phase trials have demonstrated modest ecacy of STING agonists and revealed new mechanistic and technical challenges. administration limits the use of such drugs to patients with accessible, solid tumours [ 91 ]. Mersana Apr 14, 2023 · A first-in-clinic phase 1 study of GSK3745417 STING agonist in relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndrome [abstract]. 4. While the intra-tumoral treatment was not the preferred route for treatment for the clinician. STING AGONISTS IN THE CLINC. Jan 9, 2019 · STING agonists are in clinical trials to treat patients with solid tumors. STING agonists have entered clinical trials and Feb 24, 2025 · Although several STING agonists — cyclic dinucleotides (CDNs) and non-CDNs — are currently in clinical trials, these must be injected intratumourally or intravenously. 2. The agonists aim to activate STING, with cyclic dinucleotides (CDNs) being the most common, while the inhibitors aim to block the enzymatic activity or Jul 9, 2020 · STING agonists are therefore being developed as a novel cancer therapeutic, and a greater understanding of STING pathway regulation is leading to a broadened list of candidate immune regulatory targets. Early phase clinical trials of intratumoral STING agonists are already showing promise, alone and in combination with checkpoint blockade. May 30, 2021 · The interrogation of intrinsic and adaptive resistance to cancer immunotherapy has identified lack of antigen presentation and type I interferon signaling as biomarkers of non-T-cell-inflamed tumors and clinical progression. We highlight their mechanisms, clinical trial progress, and therapeutic outcomes. Dec 31, 2022 · ADU-S100 was the first STING agonist to be examined in clinical trials to treat advanced/metastatic solid tumors and lymphomas . Very few scaffolds of 6 days ago · STING agonists associated issues like Stability, efficacy, and safety generate difficulty in clinical development [113]. In addition, transforming STING agonists into potent selective antagonists has turned out to be more challenging than expected. 18 More recent non-CDN STING agonists, such as diABZI, showed promising preclinical tumor therapeutic efficacy, 19 although their clinical efficacy and safety remain to Nov 16, 2021 · In preclinical models of exoSTING, the targeted delivery of a STING agonist to tumor resident APCs promoted localized innate immune activation, T cell attraction and expansion in the tumor, and Mar 29, 2023 · Current clinical trials with STING agonists are in the setting of advanced tumours, in which this pathway plays a complex role, promoting anti-tumour immune responses 40,44,45, cancer cell Mar 13, 2024 · Keywords: cervical cancer, tumor microenvironment, STING agonist, anti-PD-1 treatment, single-cell RNA-seq. Authors: Jacobi B Hines, Alec J Kacew, Randy F Sweis Aug 25, 2021 · Published today in Clinical Cancer Research, a journal of the American Association for Cancer Research, the study, “Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma,” describes the results of a Phase I clinical trial conducted at the Texas A&M College of Veterinary Medicine & Biomedical Sciences Jul 1, 2024 · However, these STING agonists are either in infancy with limited biological effects or have failed in clinical trials. Meric-Bernstam F, Sweis RF, Hodi FS, Messersmith WA, Andtbacka RHI, Ingham M, Lewis N, Chen X, Pelletier M, Chen X, Wu J, Dubensky TW, McWhirter SM, Müller T, Nair N Mar 13, 2023 · XMT-2056 is an Immunosynthen STING-agonist ADC that was created by leveraging a Mersana Therapeutics announces clinical hold on XMT-2056 phase 1 clinical trial. In 2020, a non-nucleotide STING agonist MSA-2 was identified, which exhibited satisfactory antitumor effects in animal studies and is amenable to oral administration. We will summarize current efforts in developing STING antagonists, describe their strength/weakness and discuss their potential for a STING drug. This protein encourages immune Jun 1, 2024 · Another STING agonist, ADC (XMT-2056), is a non-CDN STING agonist conjugated to a human epidermal growth factor receptor 2 (HER2)-targeted antibody (HT-19) binding to a novel HER2 epitope [42]. However, this was ultimately judged to add too much risk to the trial, given that the canine subjects are companion animals, when presented to the owners for consent. 3389/fimmu. Jan 16, 2025 · ABSTRACT. Firstly, i. 2023 Jul 5;29(13):2435-2444. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Jun 23, 2022 · Oncology therapies targeting the immune system have improved patient outcomes across a wide range of tumor types, but resistance due to an inadequate T-cell response in a suppressive tumor microenvironment (TME) remains a significant problem. Mar 4, 2025 · Purpose Although photothermal therapy (PTT) can induce antitumour immunity, the mechanisms underlying its effects in pancreatic cancer (PC) require further exploration. Aug 25, 2020 · STING agonists are being investigated in clinical trials, but most are based on CDNs, which exhibit poor metabolic stability and must be delivered intratumourally. Trial number Phase Treatment Patient population Status; NCT05471856 (1480-0001) 4. 31 The discovery of C202 introduces a novel avenue for the advancement of oral STING agonists, offering Due to the low cytosolic delivery of STING agonists, particularly the natural forms because of their negative charge and hydrophilic properties, most of the clinical trials administering STING agonists such as ADU-S100, E7766, and GSK3745417, use intratumoral injection. PD-1 is expressed on macrophages in the glioma microenvironment, and anti–PD-1 antibodies can induce proinflammatory M1 responses . Patients (n = 47) received weekly i. TPS2690 Engagement of the STING pathway is involved in spontaneous and treatment-induced anti-cancer immunity. . 3. kcr csbhdob jyfo znyzn trwgk flv wdbhmt glbrz qmi glb sgbufll wwt dnal fdusr fyvga