当前位置： SCI文献检索 > Science Translational Medicine期刊下所有文献 > STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade.

STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade.

Abstract：

:Stimulator of interferon genes (STING) is a cytosolic receptor that senses both exogenous and endogenous cytosolic cyclic dinucleotides (CDNs), activating TBK1/IRF3 (interferon regulatory factor 3), NF-κB (nuclear factor κB), and STAT6 (signal transducer and activator of transcription 6) signaling pathways to induce robust type I interferon and proinflammatory cytokine responses. CDN ligands were formulated with granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing cellular cancer vaccines--termed STINGVAX--that demonstrated potent in vivo antitumor efficacy in multiple therapeutic models of established cancer. We found that rationally designed synthetic CDN derivative molecules, including one with an Rp,Rp dithio diastereomer and noncanonical c[A(2',5')pA(3',5')p] phosphate bridge structure, enhanced antitumor efficacy of STINGVAX in multiple aggressive therapeutic models of established cancer in mice. Antitumor activity was STING-dependent and correlated with increased activation of dendritic cells and tumor antigen-specific CD8(+) T cells. Tumors from STINGVAX-treated mice demonstrated marked PD-L1 (programmed death ligand 1) up-regulation, which was associated with tumor-infiltrating CD8(+)IFNγ(+) T cells. When combined with PD-1 (programmed death 1) blockade, STINGVAX induced regression of palpable, poorly immunogenic tumors that did not respond to PD-1 blockade alone.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Fu J,Kanne DB,Leong M,Glickman LH,McWhirter SM,Lemmens E,Mechette K,Leong JJ,Lauer P,Liu W,Sivick KE,Zeng Q,Soares KC,Zheng L,Portnoy DA,Woodward JJ,Pardoll DM,Dubensky TW Jr,Kim Y

doi

10.1126/scitranslmed.aaa4306

subject

Has Abstract

pub_date

2015-04-15 00:00:00

pages

283ra52

issue

283

eissn

1946-6234

issn

1946-6242

pii

7/283/283ra52

journal_volume

7

pub_type

杂志文章

相关文献

Science Translational Medicine文献大全
  • SIV replication in the infected rhesus macaque is limited by the size of the preexisting TH17 cell compartment.

    abstract：:The mechanisms by which some HIV-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. Viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. However, it has been difficult ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3003941

    authors： Hartigan-O'Connor DJ,Abel K,Van Rompay KK,Kanwar B,McCune JM

    更新日期：2012-05-30 00:00:00

  • Estimating cholera incidence with cross-sectional serology.

    abstract：:The development of new approaches to cholera control relies on an accurate understanding of cholera epidemiology. However, most information on cholera incidence lacks laboratory confirmation and instead relies on surveillance systems reporting medically attended acute watery diarrhea. If recent infections could be ide...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aau6242

    authors： Azman AS,Lessler J,Luquero FJ,Bhuiyan TR,Khan AI,Chowdhury F,Kabir A,Gurwith M,Weil AA,Harris JB,Calderwood SB,Ryan ET,Qadri F,Leung DT

    更新日期：2019-02-20 00:00:00

  • Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.

    abstract：:Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SU...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3000522

    authors： Simard JM,Woo SK,Norenberg MD,Tosun C,Chen Z,Ivanova S,Tsymbalyuk O,Bryan J,Landsman D,Gerzanich V

    更新日期：2010-04-21 00:00:00

  • Striatal dopamine regulates systemic glucose metabolism in humans and mice.

    abstract：:The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting th...

    journal_title：Science translational medicine

    pub_type： 杂志文章,随机对照试验

    doi：10.1126/scitranslmed.aar3752

    authors： Ter Horst KW,Lammers NM,Trinko R,Opland DM,Figee M,Ackermans MT,Booij J,van den Munckhof P,Schuurman PR,Fliers E,Denys D,DiLeone RJ,la Fleur SE,Serlie MJ

    更新日期：2018-05-23 00:00:00

  • Lrrk2 alleles modulate inflammation during microbial infection of mice in a sex-dependent manner.

    abstract：:Variants in the leucine-rich repeat kinase-2 (LRRK2) gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested t...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aas9292

    authors： Shutinoski B,Hakimi M,Harmsen IE,Lunn M,Rocha J,Lengacher N,Zhou YY,Khan J,Nguyen A,Hake-Volling Q,El-Kodsi D,Li J,Alikashani A,Beauchamp C,Majithia J,Coombs K,Shimshek D,Marcogliese PC,Park DS,Rioux JD,Philpott D

    更新日期：2019-09-25 00:00:00

  • High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds.

    abstract：:Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolom...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aal3973

    authors： Zampieri M,Szappanos B,Buchieri MV,Trauner A,Piazza I,Picotti P,Gagneux S,Borrell S,Gicquel B,Lelievre J,Papp B,Sauer U

    更新日期：2018-02-21 00:00:00

  • Combination of an oncolytic virus with PD-L1 blockade keeps cancer in check.

    abstract：:An oncolytic vaccinia virus expressing CXCL11 combined with PD-L1 blockade significantly reduces tumor burden and improves survival in murine cancer models. ...

    journal_title：Science translational medicine

    pub_type： 评论,杂志文章

    doi：10.1126/scitranslmed.aan2781

    authors： Jonas BA

    更新日期：2017-04-19 00:00:00

  • A Mucin 16 bispecific T cell-engaging antibody for the treatment of ovarian cancer.

    abstract：:Advanced ovarian cancer is frequently treated with combination chemotherapy, but high recurrence rates show the need for therapies that can produce durable responses and extend overall survival. Bispecific antibodies that interact with tumor antigens on cancer cells and activating receptors on immune cells offer an in...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aau7534

    authors： Crawford A,Haber L,Kelly MP,Vazzana K,Canova L,Ram P,Pawashe A,Finney J,Jalal S,Chiu D,Colleton CA,Garnova E,Makonnen S,Hickey C,Krueger P,DelFino F,Potocky T,Kuhnert J,Godin S,Retter MW,Duramad P,MacDonald D,

    更新日期：2019-06-19 00:00:00

  • Could exercise metabolomics pave the way for gymnomimetics?

    abstract：:Regular physical activity and especially aerobic exercise are associated with reduced risk of disease and enhanced longevity, but the molecular mechanisms of these health benefits remain obscure. A comprehensive metabolomic approach was used to characterize the changes in blood levels of >200 metabolites upon vigorous...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3001188

    authors： Burke MF,Dunbar RL,Rader DJ

    更新日期：2010-07-21 00:00:00

  • Replacing the enzyme alpha-L-iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I.

    abstract：:Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by loss of activity of α-l-iduronidase and attendant accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate. Current treatments are suboptimal and do not address residual disease including corneal clouding, skeletal deformi...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3001380

    authors： Dierenfeld AD,McEntee MF,Vogler CA,Vite CH,Chen AH,Passage M,Le S,Shah S,Jens JK,Snella EM,Kline KL,Parkes JD,Ware WA,Moran LE,Fales-Williams AJ,Wengert JA,Whitley RD,Betts DM,Boal AM,Riedesel EA,Gross W,Ellinwo

    更新日期：2010-12-01 00:00:00

  • Quantifying prion disease penetrance using large population control cohorts.

    abstract：:More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance-the probability that a carrier of the purported disease-causing genotype will indeed develop the disease-is generally unknown. We assess the impact of variants in the prion protein gene (PRNP) on the risk of prion ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aad5169

    authors： Minikel EV,Vallabh SM,Lek M,Estrada K,Samocha KE,Sathirapongsasuti JF,McLean CY,Tung JY,Yu LP,Gambetti P,Blevins J,Zhang S,Cohen Y,Chen W,Yamada M,Hamaguchi T,Sanjo N,Mizusawa H,Nakamura Y,Kitamoto T,Collins SJ,

    更新日期：2016-01-20 00:00:00

  • Electronic consent channels: preserving patient privacy without handcuffing researchers.

    abstract：:Advances in health information technology and electronic medical records have the tremendous potential to accelerate translational and clinical research. However, privacy concerns threaten to be a rate-limiting factor. By recognizing and responding to patient privacy concerns, policy-makers, researchers, and informati...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3002037

    authors： Shelton RH

    更新日期：2011-02-09 00:00:00

  • Reversal of depressed behaviors in mice by p11 gene therapy in the nucleus accumbens.

    abstract：:The etiology of major depression remains unknown, but dysfunction of serotonergic signaling has long been implicated in the pathophysiology of this disorder. p11 is an S100 family member recently identified as a serotonin 1B [5-hydroxytryptamine 1B (5-HT(1B))] and serotonin 4 (5-HT(4)) receptor-binding protein. Mutant...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3001079

    authors： Alexander B,Warner-Schmidt J,Eriksson T,Tamminga C,Arango-Lievano M,Ghose S,Vernov M,Stavarache M,Musatov S,Flajolet M,Svenningsson P,Greengard P,Kaplitt MG

    更新日期：2010-10-20 00:00:00

  • Inflammation activation and resolution in human tendon disease.

    abstract：:Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aac4269

    authors： Dakin SG,Martinez FO,Yapp C,Wells G,Oppermann U,Dean BJ,Smith RD,Wheway K,Watkins B,Roche L,Carr AJ

    更新日期：2015-10-28 00:00:00

  • ATRAID regulates the action of nitrogen-containing bisphosphonates on bone.

    abstract：:Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical fem...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aav9166

    authors： Surface LE,Burrow DT,Li J,Park J,Kumar S,Lyu C,Song N,Yu Z,Rajagopal A,Bae Y,Lee BH,Mumm S,Gu CC,Baker JC,Mohseni M,Sum M,Huskey M,Duan S,Bijanki VN,Civitelli R,Gardner MJ,McAndrew CM,Ricci WM,Gurnett CA,D

    更新日期：2020-05-20 00:00:00

  • Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm.

    abstract：:Cardiac rhythm is extremely robust, generating 2 billion contraction cycles during the average human life span. Transcriptional control of cardiac rhythm is poorly understood. We found that removal of the transcription factor gene Tbx5 from the adult mouse caused primary spontaneous and sustained atrial fibrillation (...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aaf4891

    authors： Nadadur RD,Broman MT,Boukens B,Mazurek SR,Yang X,van den Boogaard M,Bekeny J,Gadek M,Ward T,Zhang M,Qiao Y,Martin JF,Seidman CE,Seidman J,Christoffels V,Efimov IR,McNally EM,Weber CR,Moskowitz IP

    更新日期：2016-08-31 00:00:00

  • An orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.

    abstract：:Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3008517

    authors： Krumm SA,Yan D,Hovingh ES,Evers TJ,Enkirch T,Reddy GP,Sun A,Saindane MT,Arrendale RF,Painter G,Liotta DC,Natchus MG,von Messling V,Plemper RK

    更新日期：2014-04-16 00:00:00

  • Slowing late infantile Batten disease by direct brain parenchymal administration of a rh.10 adeno-associated virus expressing CLN2.

    abstract：:Late infantile Batten disease (CLN2 disease) is an autosomal recessive, neurodegenerative lysosomal storage disease caused by mutations in the CLN2 gene encoding tripeptidyl peptidase 1 (TPP1). We tested intraparenchymal delivery of AAVrh.10hCLN2, a nonhuman serotype rh.10 adeno-associated virus vector encoding human ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.abb5413

    authors： Sondhi D,Kaminsky SM,Hackett NR,Pagovich OE,Rosenberg JB,De BP,Chen A,Van de Graaf B,Mezey JG,Mammen GW,Mancenido D,Xu F,Kosofsky B,Yohay K,Worgall S,Kaner RJ,Souwedaine M,Greenwald BM,Kaplitt M,Dyke JP,Ballon DJ

    更新日期：2020-12-02 00:00:00

  • Prospective clinical testing and experimental validation of the Pediatric Sepsis Biomarker Risk Model.

    abstract：:Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rati...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aax9000

    authors： Wong HR,Caldwell JT,Cvijanovich NZ,Weiss SL,Fitzgerald JC,Bigham MT,Jain PN,Schwarz A,Lutfi R,Nowak J,Allen GL,Thomas NJ,Grunwell JR,Baines T,Quasney M,Haileselassie B,Lindsell CJ

    更新日期：2019-11-13 00:00:00

  • Post-anesthesia AMPA receptor potentiation prevents anesthesia-induced learning and synaptic deficits.

    abstract：:Accumulating evidence has shown that repeated exposure to general anesthesia during critical stages of brain development results in long-lasting behavioral deficits later in life. To date, there has been no effective treatment to mitigate the neurotoxic effects of anesthesia on brain development. By performing calcium...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aaf7151

    authors： Huang L,Cichon J,Ninan I,Yang G

    更新日期：2016-06-22 00:00:00

  • Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

    abstract：:Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision thro...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aaa8791

    authors： Ashtari M,Zhang H,Cook PA,Cyckowski LL,Shindler KS,Marshall KA,Aravand P,Vossough A,Gee JC,Maguire AM,Baker CI,Bennett J

    更新日期：2015-07-15 00:00:00

  • Protein replacement therapies for rare diseases: a breeze for regulatory approval?

    abstract：:Protein replacement therapies for rare monogenic diseases have a higher probability of regulatory approval compared with biologics, small molecules, and grant-funded orphan drugs. ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3005007

    authors： Gorzelany JA,de Souza MP

    更新日期：2013-03-27 00:00:00

  • Patients with autism spectrum disorders display reproducible functional connectivity alterations.

    abstract：:Despite the high clinical burden, little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aat9223

    authors： Holiga Š,Hipp JF,Chatham CH,Garces P,Spooren W,D'Ardhuy XL,Bertolino A,Bouquet C,Buitelaar JK,Bours C,Rausch A,Oldehinkel M,Bouvard M,Amestoy A,Caralp M,Gueguen S,Ly-Le Moal M,Houenou J,Beckmann CF,Loth E,Murphy D

    更新日期：2019-02-27 00:00:00

  • A light-reflecting balloon catheter for atraumatic tissue defect repair.

    abstract：:A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinic...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aaa2406

    authors： Roche ET,Fabozzo A,Lee Y,Polygerinos P,Friehs I,Schuster L,Whyte W,Casar Berazaluce AM,Bueno A,Lang N,Pereira MJ,Feins E,Wasserman S,O'Cearbhaill ED,Vasilyev NV,Mooney DJ,Karp JM,Del Nido PJ,Walsh CJ

    更新日期：2015-09-23 00:00:00

  • Vitamin C puts the pedal to the metal.

    abstract：:Increased iron in cancer cells drives selective sensitization of tumors to ascorbate treatment to prolong survival. ...

    journal_title：Science translational medicine

    pub_type： 评论,杂志文章

    doi：10.1126/scitranslmed.aan2778

    authors： Venere M

    更新日期：2017-04-12 00:00:00

  • Liberating health data for clinical research applications.

    abstract：:Global investments in health information technology (HIT) in the form of electronic health record systems represent important new strategies to improve the quality and efficiency of health care. These potential benefits of HIT will not be achieved without direct attention to the use of health care information for clin...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3000764

    authors： Nadler JJ,Downing GJ

    更新日期：2010-02-10 00:00:00

  • DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates.

    abstract：:DEL-1 (developmental endothelial locus-1) is an endothelial cell-secreted protein that regulates LFA-1 (lymphocyte function-associated antigen-1) integrin-dependent leukocyte recruitment and inflammation in various tissues. We identified a novel regulatory mechanism of DEL-1 in osteoclast biology. Specifically, we sho...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aac5380

    authors： Shin J,Maekawa T,Abe T,Hajishengallis E,Hosur K,Pyaram K,Mitroulis I,Chavakis T,Hajishengallis G

    更新日期：2015-09-30 00:00:00

  • Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions.

    abstract：:The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic D...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3002001

    authors： Dombrowski Y,Peric M,Koglin S,Kammerbauer C,Göss C,Anz D,Simanski M,Gläser R,Harder J,Hornung V,Gallo RL,Ruzicka T,Besch R,Schauber J

    更新日期：2011-05-11 00:00:00

  • Rapid emergence of protease inhibitor resistance in hepatitis C virus.

    abstract：:About 170 million people worldwide are infected with hepatitis C virus (HCV). The current standard therapy leads to sustained viral elimination in only approximately 50% of the treated patients. Telaprevir, an HCV protease inhibitor, has substantial antiviral activity in patients with chronic HCV infection. However, i...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3000544

    authors： Rong L,Dahari H,Ribeiro RM,Perelson AS

    更新日期：2010-05-05 00:00:00

  • Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development.

    abstract：:Vaccines directed against the blood stages of Plasmodium falciparum malaria are intended to prevent the parasite from invading and replicating within host cells. No blood-stage malaria vaccine has shown clinical efficacy in humans. Most malaria vaccine antigens are parasite surface proteins that have evolved extensive...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3000257

    authors： Takala SL,Coulibaly D,Thera MA,Batchelor AH,Cummings MP,Escalante AA,Ouattara A,Traoré K,Niangaly A,Djimdé AA,Doumbo OK,Plowe CV

    更新日期：2009-10-14 00:00:00