STING, nanoparticles, autoimmune disease and cancer: a novel paradigm for immunotherapy?

Lemos, Henrique; Huang, Lei; McGaha, Tracy L.; Mellor, Andrew L.

doi:10.1586/1744666x.2015.995097

Cited by 18 publications

(13 citation statements)

References 72 publications

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“…What additional factors, that is, from microenvironment or immune factors contribute to the DNA release? Toll‐like receptor 9 (TLR9) is an endosomal sensor for DNA and a link between cfDNA, inflammatory disease and TLR9 has recently been reported . These and other questions to understand the biology of ctDNA release will have to be answered if cfDNA analyses should really advance to an indispensable diagnostic tool in the management of patients with cancer.…”

Section: Discussionmentioning

confidence: 99%

Patient monitoring through liquid biopsies using circulating tumor DNA

Ulz

Heitzer

Geigl

et al. 2017

Intl Journal of Cancer

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Tumors release components such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and tumor-derived extracellular vesicles into the circulation. Multiple studies have demonstrated that molecular information about tumors and metastases can be extracted from these factors, which are therefore frequently referred to as "liquid biopsies." Liquid biopsies allow the longitudinal monitoring of tumor genomes non-invasively and may hence ensure that patients receive appropriate treatments that target the molecular features of their disease. Accordingly, the number of studies employing liquid biopsy based assays has been skyrocketing in the last few years. Here, we focus on three important issues, which are of high relevance for monitoring tumor genomes. First, we analyze the relation between the allele frequency of somatic tumor-specific mutations and the tumor fraction within plasma DNA. Second, we ask how well current tumor evolution models correlate with findings in longitudinal liquid biopsy studies. And, finally, as sensitivity is one of the key challenges of mutation detection, we address the challenge of detecting mutations occurring at very low allele frequencies in plasma DNA.

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Section: Discussionmentioning

confidence: 99%

Patient monitoring through liquid biopsies using circulating tumor DNA

Ulz

Heitzer

Geigl

et al. 2017

Intl Journal of Cancer

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“…Furthermore, STING plays a role in the development of autoinflammatory diseases, cancer and other sterile inflammations [13]. However, less is known about the extent of STING and its related sensors implication in the immune responses to protozoa, fungi or helminthes.…”

Section: Stimulator Of Interferon Genes: Linking Sensing To Effectivementioning

confidence: 99%

The Emerging Roles of STING in Bacterial Infections

Marinho

Benmerzoug

Oliveira

et al. 2017

Trends in Microbiology

105

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The STING (Stimulator of Interferon Genes) protein connects micro-organism cytosolic sensing with effector functions of the host cell by sensing directly cyclic dinucleotides (CDNs), originating from pathogens or from the host upon DNA recognition. Although STING activation favors effective immune responses against viral infections, its role during bacterial diseases is controversial, ranging from protective to detrimental effects for the host. In this review, we summarize the important features of the STING activation pathway and recent highlights about the role of STING in bacterial infections caused by organisms from the Chlamydia, Listeria, Francisella, Brucella, Shigella, Salmonella, Streptococcus and Neisseria genera, with a special focus on Mycobacterium infections.

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“…Finally, we attempted to shift the anti-RT immune response to the Th1 type response by using molecular adjuvants, specifically, the mucosal adjuvant cyclic di-GMP (c-di-GMP) 75 , 76 , 78 , 110 . By using c-di-GMP, we intended to stimulate the detection of double-stranded DNA by cytosolic DNA sensors, with the induction of subsequent downstream immune signaling 111 . Indeed, the use of this adjuvant diminished anti-RT antibody responses by five fold indicating a diminished Th2 polarization.…”

Section: Discussionmentioning

confidence: 99%

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity

Latanova

Petkov

Kilpeläinen

et al. 2018

Sci Rep

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DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype DNA vaccine against drug-resistant HIV-1 based on a weak Th2-immunogen, HIV-1 reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and drug-resistant RTs (RT-DNAs) and introduced them into mice by intradermal injections followed by electroporation. RT-DNAs were administered as single or double primes with or without cyclic-di-GMP, or as a prime followed by boost with RT-DNA mixed with a luciferase-encoding plasmid (“surrogate challenge”). Repeated primes improved cellular responses and broadened epitope specificity. Addition of cyclic-di-GMP induced a transient increase in IFN-γ production. The strongest anti-RT immune response was achieved in a prime-boost protocol with electroporation by short 100V pulses done using penetrating electrodes. The RT-specific response, dominated by CD4+ T-cells, targeted epitopes at aa 199–220 and aa 528–543. Drug-resistance mutations disrupted the epitope at aa 205–220, while the CTL epitope at aa 202–210 was not affected. Overall, multiparametric optimization of RT strengthened its Th2- performance. A rapid loss of RT/luciferase-expressing cells in the surrogate challenge experiment revealed a lytic potential of anti-RT response. Such lytic CD4+ response would be beneficial for an HIV vaccine due to its comparative insensitivity to immune escape.

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STING, nanoparticles, autoimmune disease and cancer: a novel paradigm for immunotherapy?

Cited by 18 publications

References 72 publications

Patient monitoring through liquid biopsies using circulating tumor DNA

Patient monitoring through liquid biopsies using circulating tumor DNA

The Emerging Roles of STING in Bacterial Infections

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity

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