Profile of STING agonist and inhibitor research: a bibliometric analysis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 11, 2025

Background STING is a core signaling hub molecule in the innate immune system, involved various diseases, including infectious autoimmune tumors, aging, organ fibrosis, and neurodegenerative diseases. Its activation has shown great potential anti-tumor anti-infective therapies, with agonists emerging as promising approach cancer immunotherapy recent years. This study identifies research trends directions field by collecting analyzing relevant literature. Methods A total of 527 publications regarding 107 about inhibitors were retrieved from WOS Core Collection database. Bibliometric information was extracted CiteSpace VOSviewer software for visualization. Results It shows that on both burgeoning rapidly. The United States China are leading contributors this field. Application primarily focuses immunotherapy, while target inflammation, particularly neuroinflammation acute lung injury. Conclusion Current emphasizes optimizing permeability, efficacy, safety, nanotechnology lipid nanoparticles being prominent delivery techniques. Future expected to focus drug development clinical applications. comprehensive bibliometric analysis provides insights guide further investigation agonist/inhibitor.

Language: Английский

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Targeting cGAS-STING pathway for reprogramming tumor-associated macrophages to enhance anti-tumor immunotherapy

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 12, 2025

Abstract The cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) signaling pathway plays a crucial role in activating innate and specific immunity anti-tumor immunotherapy. As the major infiltrating cells tumor microenvironment (TME), tumor-associated macrophages (TAMs) could be polarized into either M1 or pro-tumor M2 types based on various stimuli. Accordingly, targeted reprogramming TAMs to restore immune balance shows promise as an effective strategy. In this review, we aim target cGAS-STING for enhance We investigated double-edged sword effects of regulating TME. regulative roles its impact TME were further revealed. More importantly, several strategies targeting designed enhancing Taken together, might promising strategy

Language: Английский

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A Cyclic-di-AMP Adjuvanted CPAF Protein Vaccine Is Immunogenic in Swine, but It Fails to Reduce Genital Chlamydia trachomatis Burden

Vaccines, Journal Year: 2025, Volume and Issue: 13(5), P. 468 - 468

Published: April 27, 2025

Background/Objectives: Chlamydia trachomatis (Ct) is the leading bacterial cause of sexually transmitted infection globally. If undiagnosed or left untreated, these infections can lead to serious complications such as infertility, ectopic pregnancies, and chronic pelvic pain. Despite high prevalence potential for health complications, no vaccine has been licensed. Pigs offer a valuable biomedical model chlamydia research: they have an overall degree similarity humans serve natural hosts suis (Cs), close relative Ct. Thus, in this study, pig was used evaluate candidate against Methods: The consists chlamydial-protease-like activity factor (CPAF) protein adjuvanted with STING (Stimulator Interferon Genes) pathway agonist cyclic-di-AMP (c-di-AMP). received two doses intramuscularly followed by intranasal doses. Each week, systemic T cell response assessed via IFN-γ IL-17 ELISpots, well multi-parameter flow cytometry on 0, 14, 28 days post vaccination (dpv). humoral immune analyzed measuring CPAF-specific antibody levels avidity ELISAs. Results: Vaccination c-di-AMP CPAF triggered low-level multifunctional IFN-γ+TNF-α+ CD4 responses. rather low effector cytokine production, robust anti-CPAF IgG responses were detected serum, vaginal swab eluates, oviduct flushes. Genital Ct challenge 42 dpv resulted only transient infection, precluding confident assessment efficacy tested CPAF/c-di-AMP candidate. However, after challenge, vaccinated pigs exhibited boosted mucosal compared unvaccinated pigs. Conclusions: while remains elusive, immunogenic: it elicited cell-mediated Future studies will incorporate directly conjugated addition other Th1-inducing adjuvants enhance cellular immunity.

Language: Английский

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Democratizing FLASH Radiotherapy

Seminars in Radiation Oncology, Journal Year: 2024, Volume and Issue: 34(3), P. 344 - 350

Published: June 15, 2024

FLASH radiotherapy (RT) is emerging as a potentially revolutionary advancement in cancer treatment, offering the potential to deliver RT at ultra-high dose rates (>40 Gy/s) while significantly reducing damage healthy tissues. Democratizing by making this cutting-edge approach more accessible and affordable for healthcare systems worldwide would have substantial impact global health. Here, we review recent developments present perspective on further that could facilitate democratizing of RT. These include upgrading validating current technologies can measure radiation with high accuracy precision, establishing deeper mechanistic understanding effect, optimizing delivery conditions parameters different types tumors normal tissues, such rate, fractionation, beam quality efficacy. Furthermore, examine radioimmunotherapy leveraging evidence make tumor microenvironment immunogenic, parallel nanomedicine or use smart biomaterials combining immunotherapy. We conclude democratization represents major opportunity concerted cross-disciplinary research collaborations tremendous disparities extending moonshot globally.

Language: Английский

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cGAS/STING in skin melanoma: from molecular mechanisms to therapeutics

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 18, 2024

Language: Английский

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Metal–Phenolic Network Hydrogel Vaccine Platform for Enhanced Humoral Immunity against Lethal Rabies Virus

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 2, 2025

Rabies, caused by rabies virus (RABV), is a zoonotic disease with high mortality rate that has attracted global attention the goal of eradication 2030. However, can only be prevented appropriate and multiple vaccinations, which impede widespread vaccination in developing countries due to its expenditure. Designing single-dose vaccines pressing challenge prevention other infectious diseases. Herein, metal-phenolic network (MPN)-based hydrogel vaccine (designated as CGMR) was developed stimulate potent humoral immunity against RABV infection single immunization, resulting 4.3-fold 1.8-fold enhancements virus-neutralizing antibody compared induced inactivated alum adjuvant. The CGMR, cross-linked phenol-modified chitosan manganese ion, could prolong residence time confining antigen hydrogel, acting "hydrogel depot". It also stimulated activation cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator interferon gene (STING) pathway, facilitating dendritic cell maturation presentation. formulation recruited immunocytes activated germinal center, enhancing sustaining immune responses virulent challenge. Collectively, this injectable manganese-based provides universal ideal avenue for

Language: Английский

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Opportunities and Challenges for Nanomaterials as Vaccine Adjuvants

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract Adjuvants, as a critical component of vaccines, are capable eliciting more robust and sustained immune responses. Nanomaterials have shown unique advantages broad application prospects in adjuvant development due to their high adjustability distinctive physicochemical properties. This review focuses on nanoadjuvants immunological mechanisms. First, various types adjuvants introduced with an emphasis metal oxide nanoparticles, coordination polymers, liposomes, polymer other inorganic nanoparticles that can serve vaccine adjuvants. Second, this describes the current status clinical applications nanoadjuvants. Next, mechanisms action for been thoroughly elucidated, including depot effect, NLRP3 inflammasome activation, targeting C‐type lectin receptors, activation toll‐like cGAS‐STING signaling pathway. Finally, challenges opportunities associated also addressed.

Language: Английский

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Mn and Zn-Doped Multivariate Metal-Organic Framework as a Metalloimmunological Adjuvant to Promote Protection Against Tuberculosis Infection

Published: May 29, 2024

A first-in-class vaccine adjuvant delivery system, Mn-ZIF, was developed by incorporating manganese (Mn) into the zinc-containing zeolitic-imidazolate framework-8 (ZIF-8). The mixed metal approach, which allowed for tunable Mn doping, made possible including a mild reducing agent reaction mixture. This approach up to 50% Mn, with remaining Zn within ZIF. multivariate exhibited significantly decreased cytotoxicity compared ZIF-8. porous structure of Mn-ZIF enabled co-delivery STING agonist cyclic di-adenosine monophosphate (CDA) through post-synthetic loading, forming CDA@Mn-ZIF. composite demonstrated enhanced cellular uptake and synergistic activation cGAS-STING pathway, producing proinflammatory cytokines activating antigen-presenting cells (APCs). In preclinical Mycobacterium tuberculosis (Mtb) model, CDA@Mn-ZIF formulated CysVac2 fusion protein elicited potent antigen-specific T-cell response reduced mycobacterial burden in lungs infected mice. These findings highlight potential as promising subunit vaccines, offering novel enhancing efficacy protection against infectious diseases such tuberculosis.

Language: Английский

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The cGAS/STING Pathway—A New Potential Biotherapeutic Target for Gastric Cancer?

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(7), P. 736 - 736

Published: July 9, 2024

Gastric cancer ranks among the top five deadliest tumors worldwide, both in terms of prevalence and mortality rates. Despite mainstream treatments, efficacy treating gastric remains suboptimal, underscoring urgency for novel therapeutic approaches. The elucidation tumor immunosuppressive microenvironments has shifted focus towards biotherapeutics, which leverage patient’s immune system or biologics to target cells. Biotherapy emerged as a promising alternative resistant traditional chemotherapy, radiation, immunotherapy. Central this paradigm is cGAS-STING pathway, pivotal component innate system. This pathway recognizes aberrant DNA, such that from viral infections cells, triggers an response, thereby reshaping microenvironment into immune-stimulating milieu. In context cancer, harnessing holds significant potential biotherapeutic interventions. review provides comprehensive overview latest research on including insights clinical trials involving STING agonists. Furthermore, it assesses prospects targeting strategy cancer.

Language: Английский

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The adjuvant effect of manganese on tuberculosis subunit vaccine Bfrb-GrpE

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: Dec. 19, 2024

Protein subunit vaccines, lacking pathogen-associated molecular patterns that trigger immune responses, rely on adjuvants to induce robust responses against the target pathogen. Thus, selection of plays a crucial role in design protein vaccines. Recently, there has been growing interest utilizing cGAS-STING agonists as vaccine adjuvants. In this study, we investigated adjuvant effect manganese (Mn), agonist, tuberculosis Bfrb-GrpE (BG) mouse model. Initially, mice were administered with BG-Mn(J), and its immunogenicity protective efficacy assessed six weeks after final immunization. The results showed Mn(J) enhanced both cellular humoral BG conferred effective protection M. H37Ra infection mice, leading significant reduction 2.0 ± 0.17 Log10 CFU spleens 1.3 lungs compared PBS control group. Additionally, BG-Mn(J) surrogate model rabbit skin vaccination also provided model, indicated by decreased bacterial load at site, minimal pathological damage, accelerated healing. These findings suggest holds promise an for underscoring potential enhance offer infection.

Language: Английский

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