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Trial watch: STING agonists in cancer therapy.

作者信息

Le Naour Julie, Zitvogel Laurence, Galluzzi Lorenzo, Vacchelli Erika, Kroemer Guido

机构信息

Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM, Centre de Recherche des Cordeliers, Paris, France.

Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.

出版信息

Oncoimmunology. 2020 Jun 16;9(1):1777624. doi: 10.1080/2162402X.2020.1777624.


DOI:10.1080/2162402X.2020.1777624
PMID:32934881
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7466854/
Abstract

Stimulator of interferon response cGAMP interactor 1 (STING1, best known as STING) is an endoplasmic reticulum-sessile protein that serves as a signaling hub, receiving input from several pattern recognition receptors, most of which sense ectopic DNA species in the cytosol. In particular, STING ensures the production of type I interferon (IFN) in response to invading DNA viruses, bacterial pathogens, as well as DNA leaking from mitochondria or the nucleus (., in cells exposed to chemotherapy or radiotherapy). As a type I IFN is critical for the initiation of anticancer immune responses, the pharmaceutical industry has generated molecules that directly activate STING for use in oncological indications. 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. In this Trial Watch, we discuss preclinical evidence and accumulating clinical experience shaping the design of Phase I and Phase II trials that evaluate the safety and preliminary efficacy of STING agonists in cancer patients.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547a/7466854/d341d20cab86/KONI_A_1777624_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547a/7466854/d341d20cab86/KONI_A_1777624_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547a/7466854/d341d20cab86/KONI_A_1777624_F0001_OC.jpg

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[3]
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[4]
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[5]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling.

Nat Immunol. 2020-3-30

[2]
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death.

J Immunother Cancer. 2020-3

[3]
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Oncoimmunology. 2020-2-9

[4]
Checkpoint molecules coordinately restrain hyperactivated effector T cells in the tumor microenvironment.

Oncoimmunology. 2020-1-30

[5]
In the mix: the potential benefits of adding GM-CSF to CpG-B in the local treatment of patients with early-stage melanoma.

Oncoimmunology. 2019-12-26

[6]
The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non-small-cell lung cancer: a real-life retrospective study.

Oncoimmunology. 2019-11-5

[7]
Human DNA-PK activates a STING-independent DNA sensing pathway.

Sci Immunol. 2020-1-24

[8]
STING-dependent paracriny shapes apoptotic priming of breast tumors in response to anti-mitotic treatment.

Nat Commun. 2020-1-14

[9]
Immunological impact of cell death signaling driven by radiation on the tumor microenvironment.

Nat Immunol. 2019-12-23

[10]
Type I interferons and dendritic cells in cancer immunotherapy.

Int Rev Cell Mol Biol. 2019-6-20

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