Overcoming STING Agonists Barriers: Peptide, Protein, and Biomembrane‐based Biocompatible Delivery Strategies

Zheng, Yongfang; Wu, Jun

doi:10.1002/asia.202101400

Cited by 4 publications

(8 citation statements)

References 62 publications

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“…161 Peptide sequences are designed to allow charged small molecule drugs to be incorporated through nanofiber cross-linking for extended release, potentially improving the efficacy of CDNs in challenging, refractory tumor models. 162,163…”

Section: Peptide-based Strategiesmentioning

confidence: 99%

“…STING-based ADC drugs address the systemic toxicity drawbacks of small-molecule STING agonists and demonstrate targeted delivery into multiple tumor tissues. 162,164 Notably, TAK-500 by Takeda 165 and XMT-2056 by Mersana 166 are both in phase 1 clinical trials. Meanwhile, JAB-X1800 by Jacobio Pharmaceuticals 167 is undergoing preclinical studies, and F-star Therapeutic has also disclosed their preclinical study on an ADC with STING agonist.…”

Section: Protein-based Strategiesmentioning

confidence: 99%

“…Preclinical data reveal that XMT-2056 exhibits potent STING activity with over a 100-fold improvement in activity compared to the free STING-agonist payload. 162,166 Except for antibodies, other proteins can also be utilized to deliver agonists. Human heavy chain ferritin NPs disassemble into subunits when the pH is lowered to 2-3 and reassemble to an almost original form when the pH returns to physiological conditions.…”

Section: Protein-based Strategiesmentioning

confidence: 99%

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cGAS‐STING pathway agonists are promising vaccine adjuvants

Tian,

Ai,

Tian

et al. 2024

Medicinal Research Reviews

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Adjuvants are of critical value in vaccine development as they act on enhancing immunogenicity of antigen and inducing long‐lasting immunity. However, there are only a few adjuvants that have been approved for clinical use, which highlights the need for exploring and developing new adjuvants to meet the growing demand for vaccination. Recently, emerging evidence demonstrates that the cGAS‐STING pathway orchestrates innate and adaptive immunity by generating type I interferon responses. Many cGAS‐STING pathway agonists have been developed and tested in preclinical research for the treatment of cancer or infectious diseases with promising results. As adjuvants, cGAS‐STING agonists have demonstrated their potential to activate robust defense immunity in various diseases, including COVID‐19 infection. This review summarized the current developments in the field of cGAS‐STING agonists with a special focus on the latest applications of cGAS‐STING agonists as adjuvants in vaccination. Potential challenges were also discussed in the hope of sparking future research interests to further the development of cGAS‐STING as vaccine adjuvants.

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Section: Peptide-based Strategiesmentioning

confidence: 99%

Section: Protein-based Strategiesmentioning

confidence: 99%

Section: Protein-based Strategiesmentioning

confidence: 99%

See 1 more Smart Citation

cGAS‐STING pathway agonists are promising vaccine adjuvants

Tian,

Ai,

Tian

et al. 2024

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…Several STING agonists are currently under clinical investigation ( Table 1 ). STING agonists, which include cyclic dinucleotides (CDNs) and their derivatives ( 125 ), non-CDN small-molecule agonists ( 126 ), and antibody-drug conjugates, represent a groundbreaking class of small-molecule intrinsic immune agonists ( 127 ). The low molecular weight of STING agonists enables high tumor distribution through systemic administration.…”

Section: Application Of Sting Agonists In Cancer Researchmentioning

confidence: 99%

GAS-STING: a classical DNA recognition pathways to tumor therapy

Wang,

Lin,

Zhu

et al. 2023

Front. Immunol.

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Cyclic GMP-AMP synthetase (cGAS), recognized as the primary DNA sensor within cells, possesses the capability to identify foreign DNA molecules along with free DNA fragments. This identification process facilitates the production of type I IFNs through the activator of the interferon gene (STING) which induces the phosphorylation of downstream transcription factors. This action characterizes the most archetypal biological functionality of the cGAS-STING pathway. When treated with anti-tumor agents, cells experience DNA damage that triggers activation of the cGAS-STING pathway, culminating in the expression of type I IFNs and associated downstream interferon-stimulated genes. cGAS-STING is one of the important innate immune pathways,the role of type I IFNs in the articulation between innate immunity and T-cell antitumour immunity.type I IFNs promote the recruitment and activation of inflammatory cells (including NK cells) at the tumor site.Type I IFNs also can promote the activation and maturation of dendritic cel(DC), improve the antigen presentation of CD4+T lymphocytes, and enhance the cross-presentation of CD8+T lymphocytes to upregulating anti-tumor responses. This review discussed the cGAS-STING signaling and its mechanism and biological function in traditional tumor therapy and immunotherapy.

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“…For nearly a century, Aluminum-containing adjuvants have been utilized to boost immune responses in the billions of doses of vaccines. Along with the evolution of the biocompatible platforms of peptide, protein and biomembrane, the stability of STING agonists has been improved ( 80 ). So far, only a few adjuvants have been approved for humans use, of which aluminum-containing adjuvant is the only one widely used ( 81 ).…”

Section: Therapeutic Drugs Targeting Stingmentioning

confidence: 99%

Progress of cGAS-STING signaling in response to SARS-CoV-2 infection

Zhang

Yuan

et al. 2022

Front. Immunol.

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Coronavirus disease 2019 (COVID-19) is an epidemic respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can cause infections in millions of individuals, who can develop lung injury, organ failure, and subsequent death. As the first line of host defense, the innate immune system is involved in initiating the immune response to SARS-CoV-2 infection and the hyperinflammatory phenotype of COVID-19. However, the interplay between SARS-CoV-2 and host innate immunity is not yet well understood. It had become known that the cGAS-STING pathway is involved in the detection of cytosolic DNA, which elicits an innate immune response involving a robust type I interferon response against viral and bacterial infections. Nevertheless, several lines of evidence indicate that SARS-CoV-2, a single-stranded positive-sense RNA virus, triggered the cGAS-STING signaling pathway. Therefore, understanding the molecular and cellular details of cGAS-STING signaling upon SARS-CoV-2 infection is of considerable biomedical importance. In this review, we discuss the role of cGAS-STING signaling in SARS-CoV-2 infection and summarize the potential therapeutics of STING agonists as virus vaccine adjuvants.

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Overcoming STING Agonists Barriers: Peptide, Protein, and Biomembrane‐based Biocompatible Delivery Strategies

Cited by 4 publications

References 62 publications

cGAS‐STING pathway agonists are promising vaccine adjuvants

cGAS‐STING pathway agonists are promising vaccine adjuvants

GAS-STING: a classical DNA recognition pathways to tumor therapy

Progress of cGAS-STING signaling in response to SARS-CoV-2 infection

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