Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

J. Scott Crowe, Kevin J. Roberts, Timothy M. Carlton, Luana Maggiore, Marion F. Cubitt, Simon Clare, Katherine Harcourt, Jill Reckless, Thomas T. MacDonald, Keith P. Ray, Anna Vossenkämper, Michael R. West

ABSTRACT

TNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNFα-TNFα receptor-binding ELISAs as well as TNFα responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNFα with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed naïve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not naïve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised. More... »

PAGES

4941

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-23277-7

DOI

http://dx.doi.org/10.1038/s41598-018-23277-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101598184

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29563546


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1115", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Pharmacology and Pharmaceutical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "VHsquared (United Kingdom)", 
          "id": "https://www.grid.ac/institutes/grid.439102.d", 
          "name": [
            "VHsquared Ltd., 1 Lower Court, Copley Hill, Cambridge Road, Babraham, CB22 3GN, Cambridge, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Crowe", 
        "givenName": "J. Scott", 
        "id": "sg:person.011254767474.28", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011254767474.28"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "VHsquared (United Kingdom)", 
          "id": "https://www.grid.ac/institutes/grid.439102.d", 
          "name": [
            "VHsquared Ltd., 1 Lower Court, Copley Hill, Cambridge Road, Babraham, CB22 3GN, Cambridge, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Roberts", 
        "givenName": "Kevin J.", 
        "id": "sg:person.01115547515.71", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01115547515.71"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "VHsquared (United Kingdom)", 
          "id": "https://www.grid.ac/institutes/grid.439102.d", 
          "name": [
            "VHsquared Ltd., 1 Lower Court, Copley Hill, Cambridge Road, Babraham, CB22 3GN, Cambridge, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Carlton", 
        "givenName": "Timothy M.", 
        "id": "sg:person.07570154354.80", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07570154354.80"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "VHsquared (United Kingdom)", 
          "id": "https://www.grid.ac/institutes/grid.439102.d", 
          "name": [
            "VHsquared Ltd., 1 Lower Court, Copley Hill, Cambridge Road, Babraham, CB22 3GN, Cambridge, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Maggiore", 
        "givenName": "Luana", 
        "id": "sg:person.011163115354.39", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011163115354.39"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "VHsquared (United Kingdom)", 
          "id": "https://www.grid.ac/institutes/grid.439102.d", 
          "name": [
            "VHsquared Ltd., 1 Lower Court, Copley Hill, Cambridge Road, Babraham, CB22 3GN, Cambridge, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cubitt", 
        "givenName": "Marion F.", 
        "id": "sg:person.0605072567.45", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605072567.45"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wellcome Sanger Institute", 
          "id": "https://www.grid.ac/institutes/grid.10306.34", 
          "name": [
            "Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA, Hinxton, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Clare", 
        "givenName": "Simon", 
        "id": "sg:person.01172611216.14", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01172611216.14"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wellcome Sanger Institute", 
          "id": "https://www.grid.ac/institutes/grid.10306.34", 
          "name": [
            "Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA, Hinxton, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Harcourt", 
        "givenName": "Katherine", 
        "id": "sg:person.01013163164.88", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01013163164.88"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Babraham Institute", 
          "id": "https://www.grid.ac/institutes/grid.418195.0", 
          "name": [
            "RxCelerate Ltd. Babraham Research Campus, CB22 3AT, Cambridge, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Reckless", 
        "givenName": "Jill", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Queen Mary University of London", 
          "id": "https://www.grid.ac/institutes/grid.4868.2", 
          "name": [
            "Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, E1 2AT, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "MacDonald", 
        "givenName": "Thomas T.", 
        "id": "sg:person.012002024422.00", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012002024422.00"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "VHsquared (United Kingdom)", 
          "id": "https://www.grid.ac/institutes/grid.439102.d", 
          "name": [
            "VHsquared Ltd., 1 Lower Court, Copley Hill, Cambridge Road, Babraham, CB22 3GN, Cambridge, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ray", 
        "givenName": "Keith P.", 
        "id": "sg:person.013770050630.06", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013770050630.06"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Queen Mary University of London", 
          "id": "https://www.grid.ac/institutes/grid.4868.2", 
          "name": [
            "Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, E1 2AT, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Vossenk\u00e4mper", 
        "givenName": "Anna", 
        "id": "sg:person.01337572626.38", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01337572626.38"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "VHsquared (United Kingdom)", 
          "id": "https://www.grid.ac/institutes/grid.439102.d", 
          "name": [
            "VHsquared Ltd., 1 Lower Court, Copley Hill, Cambridge Road, Babraham, CB22 3GN, Cambridge, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "West", 
        "givenName": "Michael R.", 
        "id": "sg:person.01153374015.78", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01153374015.78"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/mi.2009.116", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001891413", 
          "https://doi.org/10.1038/mi.2009.116"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/mi.2009.116", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001891413", 
          "https://doi.org/10.1038/mi.2009.116"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.pathophys.2014.05.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002304542"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0028218", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003321057"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.3462", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004168882", 
          "https://doi.org/10.1038/nm.3462"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/mib.0b013e3182a11958", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005155636"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/mib.0b013e3182a11958", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005155636"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1136/gut.2004.047092", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005443029"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1111/j.1572-0241.2002.05914.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007520375", 
          "https://doi.org/10.1111/j.1572-0241.2002.05914.x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1155/2012/718617", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009458252"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10620-015-4007-z", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015197824", 
          "https://doi.org/10.1007/s10620-015-4007-z"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s003840050181", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018960758", 
          "https://doi.org/10.1007/s003840050181"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-biochem-063011-092449", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022495591"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.gastro.2014.03.049", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022952212"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.gastro.2015.07.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023481453"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1023/a:1005554900286", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026513664", 
          "https://doi.org/10.1023/a:1005554900286"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cgh.2015.10.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026803848"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00253-005-0300-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027756420", 
          "https://doi.org/10.1007/s00253-005-0300-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00253-005-0300-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027756420", 
          "https://doi.org/10.1007/s00253-005-0300-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/protein/gzu011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029398507"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.gastro.2011.08.032", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036485440"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/mi.2012.4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039750426", 
          "https://doi.org/10.1038/mi.2012.4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10875-009-9323-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043771900", 
          "https://doi.org/10.1007/s10875-009-9323-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10875-009-9323-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043771900", 
          "https://doi.org/10.1007/s10875-009-9323-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0016-5085(99)70551-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051709830"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0016-5085(99)70551-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051709830"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmct1209614", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053524613"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ja3061276", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055852951"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/ecco-jcc/jjw026", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059495253"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/ecco-jcc/jjw036", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059495261"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/ecco-jcc/jjw053", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059495273"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1756283x15576462", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064076555"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1756283x15576462", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064076555"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3748/wjg.v22.i42.9300", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071374145"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/mabs.12304", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072305518"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jcmgh.2017.03.007", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084086244"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jim.2017.03.023", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084528572"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3389/fimmu.2017.00867", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1090931878"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-12", 
    "datePublishedReg": "2018-12-01", 
    "description": "TNF\u03b1 is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNF\u03b1 domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNF\u03b1-TNF\u03b1 receptor-binding ELISAs as well as TNF\u03b1 responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNF\u03b1 with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed na\u00efve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not na\u00efve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41598-018-23277-7", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2770727", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1045337", 
        "issn": [
          "2045-2322"
        ], 
        "name": "Scientific Reports", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "8"
      }
    ], 
    "name": "Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease", 
    "pagination": "4941", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "11bbbfe4538414dbe903c9c1293471da7e992a945119dc284f63bfe701f6bde3"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29563546"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101563288"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41598-018-23277-7"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1101598184"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41598-018-23277-7", 
      "https://app.dimensions.ai/details/publication/pub.1101598184"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T13:18", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000368_0000000368/records_78950_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41598-018-23277-7"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-23277-7'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-23277-7'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-23277-7'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-23277-7'


 

This table displays all metadata directly associated to this object as RDF triples.

260 TRIPLES      21 PREDICATES      61 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41598-018-23277-7 schema:about anzsrc-for:11
2 anzsrc-for:1115
3 schema:author N2c9b17425c6c4358b414e2bbcb393f2c
4 schema:citation sg:pub.10.1007/s00253-005-0300-7
5 sg:pub.10.1007/s003840050181
6 sg:pub.10.1007/s10620-015-4007-z
7 sg:pub.10.1007/s10875-009-9323-7
8 sg:pub.10.1023/a:1005554900286
9 sg:pub.10.1038/mi.2009.116
10 sg:pub.10.1038/mi.2012.4
11 sg:pub.10.1038/nm.3462
12 sg:pub.10.1111/j.1572-0241.2002.05914.x
13 https://doi.org/10.1016/j.cgh.2015.10.025
14 https://doi.org/10.1016/j.jcmgh.2017.03.007
15 https://doi.org/10.1016/j.jim.2017.03.023
16 https://doi.org/10.1016/j.pathophys.2014.05.002
17 https://doi.org/10.1016/s0016-5085(99)70551-2
18 https://doi.org/10.1021/ja3061276
19 https://doi.org/10.1053/j.gastro.2011.08.032
20 https://doi.org/10.1053/j.gastro.2014.03.049
21 https://doi.org/10.1053/j.gastro.2015.07.002
22 https://doi.org/10.1056/nejmct1209614
23 https://doi.org/10.1093/ecco-jcc/jjw026
24 https://doi.org/10.1093/ecco-jcc/jjw036
25 https://doi.org/10.1093/ecco-jcc/jjw053
26 https://doi.org/10.1093/protein/gzu011
27 https://doi.org/10.1097/mib.0b013e3182a11958
28 https://doi.org/10.1136/gut.2004.047092
29 https://doi.org/10.1146/annurev-biochem-063011-092449
30 https://doi.org/10.1155/2012/718617
31 https://doi.org/10.1177/1756283x15576462
32 https://doi.org/10.1371/journal.pone.0028218
33 https://doi.org/10.3389/fimmu.2017.00867
34 https://doi.org/10.3748/wjg.v22.i42.9300
35 https://doi.org/10.4161/mabs.12304
36 schema:datePublished 2018-12
37 schema:datePublishedReg 2018-12-01
38 schema:description TNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNFα-TNFα receptor-binding ELISAs as well as TNFα responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNFα with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed naïve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not naïve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised.
39 schema:genre research_article
40 schema:inLanguage en
41 schema:isAccessibleForFree true
42 schema:isPartOf Ndba1e8b684f1423490265b1892bfd2b6
43 Ndca37c93c18b44ec962b7081353adce1
44 sg:journal.1045337
45 schema:name Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease
46 schema:pagination 4941
47 schema:productId N0b4f45d6507542458428fff869ec1b9c
48 N7a8bd7112373496b8106b0bbe3593b36
49 N9f8703347ebb4325bbd83005fae5470d
50 Nab93bd9f5fd4483bb8792ab4be517b63
51 Nef5852d6260a4f5f803d50709db3e579
52 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101598184
53 https://doi.org/10.1038/s41598-018-23277-7
54 schema:sdDatePublished 2019-04-11T13:18
55 schema:sdLicense https://scigraph.springernature.com/explorer/license/
56 schema:sdPublisher Nbd4f569854f14d64a772c1a5ac8a0f5c
57 schema:url https://www.nature.com/articles/s41598-018-23277-7
58 sgo:license sg:explorer/license/
59 sgo:sdDataset articles
60 rdf:type schema:ScholarlyArticle
61 N0b4f45d6507542458428fff869ec1b9c schema:name pubmed_id
62 schema:value 29563546
63 rdf:type schema:PropertyValue
64 N2c9b17425c6c4358b414e2bbcb393f2c rdf:first sg:person.011254767474.28
65 rdf:rest N4fec1f2349e442d2a4b8b33b62cbb9c3
66 N4fec1f2349e442d2a4b8b33b62cbb9c3 rdf:first sg:person.01115547515.71
67 rdf:rest N82c7b0296f98430e92317b6f5dadc86e
68 N5a4a5a84d7954e0187be1af016c9a0d3 rdf:first sg:person.01337572626.38
69 rdf:rest N9cd8430bda064d619c3c9343886afc57
70 N5bfad16b651d408b9e7b4876cac3867f schema:affiliation https://www.grid.ac/institutes/grid.418195.0
71 schema:familyName Reckless
72 schema:givenName Jill
73 rdf:type schema:Person
74 N617bc31c9c7c416da87f06b615b4af04 rdf:first sg:person.013770050630.06
75 rdf:rest N5a4a5a84d7954e0187be1af016c9a0d3
76 N6180e7a0db954e3e80ffc6e2289aad3f rdf:first sg:person.01013163164.88
77 rdf:rest N94152bb0d1f84e72bc7dcd3ac91bde24
78 N63dc1e0da0104eb28e261c3247ffea8a rdf:first sg:person.01172611216.14
79 rdf:rest N6180e7a0db954e3e80ffc6e2289aad3f
80 N7a8bd7112373496b8106b0bbe3593b36 schema:name nlm_unique_id
81 schema:value 101563288
82 rdf:type schema:PropertyValue
83 N82c7b0296f98430e92317b6f5dadc86e rdf:first sg:person.07570154354.80
84 rdf:rest Nab3a0805289645c8bf3a1e3533d1134b
85 N94152bb0d1f84e72bc7dcd3ac91bde24 rdf:first N5bfad16b651d408b9e7b4876cac3867f
86 rdf:rest Naf7835fe1fff41b188803776d97e4e91
87 N9cd8430bda064d619c3c9343886afc57 rdf:first sg:person.01153374015.78
88 rdf:rest rdf:nil
89 N9f8703347ebb4325bbd83005fae5470d schema:name doi
90 schema:value 10.1038/s41598-018-23277-7
91 rdf:type schema:PropertyValue
92 Nab3a0805289645c8bf3a1e3533d1134b rdf:first sg:person.011163115354.39
93 rdf:rest Nd092e2bd976947f299292ea3be8b0d8f
94 Nab93bd9f5fd4483bb8792ab4be517b63 schema:name readcube_id
95 schema:value 11bbbfe4538414dbe903c9c1293471da7e992a945119dc284f63bfe701f6bde3
96 rdf:type schema:PropertyValue
97 Naf7835fe1fff41b188803776d97e4e91 rdf:first sg:person.012002024422.00
98 rdf:rest N617bc31c9c7c416da87f06b615b4af04
99 Nbd4f569854f14d64a772c1a5ac8a0f5c schema:name Springer Nature - SN SciGraph project
100 rdf:type schema:Organization
101 Nd092e2bd976947f299292ea3be8b0d8f rdf:first sg:person.0605072567.45
102 rdf:rest N63dc1e0da0104eb28e261c3247ffea8a
103 Ndba1e8b684f1423490265b1892bfd2b6 schema:volumeNumber 8
104 rdf:type schema:PublicationVolume
105 Ndca37c93c18b44ec962b7081353adce1 schema:issueNumber 1
106 rdf:type schema:PublicationIssue
107 Nef5852d6260a4f5f803d50709db3e579 schema:name dimensions_id
108 schema:value pub.1101598184
109 rdf:type schema:PropertyValue
110 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
111 schema:name Medical and Health Sciences
112 rdf:type schema:DefinedTerm
113 anzsrc-for:1115 schema:inDefinedTermSet anzsrc-for:
114 schema:name Pharmacology and Pharmaceutical Sciences
115 rdf:type schema:DefinedTerm
116 sg:grant.2770727 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-018-23277-7
117 rdf:type schema:MonetaryGrant
118 sg:journal.1045337 schema:issn 2045-2322
119 schema:name Scientific Reports
120 rdf:type schema:Periodical
121 sg:person.01013163164.88 schema:affiliation https://www.grid.ac/institutes/grid.10306.34
122 schema:familyName Harcourt
123 schema:givenName Katherine
124 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01013163164.88
125 rdf:type schema:Person
126 sg:person.01115547515.71 schema:affiliation https://www.grid.ac/institutes/grid.439102.d
127 schema:familyName Roberts
128 schema:givenName Kevin J.
129 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01115547515.71
130 rdf:type schema:Person
131 sg:person.011163115354.39 schema:affiliation https://www.grid.ac/institutes/grid.439102.d
132 schema:familyName Maggiore
133 schema:givenName Luana
134 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011163115354.39
135 rdf:type schema:Person
136 sg:person.011254767474.28 schema:affiliation https://www.grid.ac/institutes/grid.439102.d
137 schema:familyName Crowe
138 schema:givenName J. Scott
139 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011254767474.28
140 rdf:type schema:Person
141 sg:person.01153374015.78 schema:affiliation https://www.grid.ac/institutes/grid.439102.d
142 schema:familyName West
143 schema:givenName Michael R.
144 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01153374015.78
145 rdf:type schema:Person
146 sg:person.01172611216.14 schema:affiliation https://www.grid.ac/institutes/grid.10306.34
147 schema:familyName Clare
148 schema:givenName Simon
149 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01172611216.14
150 rdf:type schema:Person
151 sg:person.012002024422.00 schema:affiliation https://www.grid.ac/institutes/grid.4868.2
152 schema:familyName MacDonald
153 schema:givenName Thomas T.
154 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012002024422.00
155 rdf:type schema:Person
156 sg:person.01337572626.38 schema:affiliation https://www.grid.ac/institutes/grid.4868.2
157 schema:familyName Vossenkämper
158 schema:givenName Anna
159 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01337572626.38
160 rdf:type schema:Person
161 sg:person.013770050630.06 schema:affiliation https://www.grid.ac/institutes/grid.439102.d
162 schema:familyName Ray
163 schema:givenName Keith P.
164 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013770050630.06
165 rdf:type schema:Person
166 sg:person.0605072567.45 schema:affiliation https://www.grid.ac/institutes/grid.439102.d
167 schema:familyName Cubitt
168 schema:givenName Marion F.
169 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605072567.45
170 rdf:type schema:Person
171 sg:person.07570154354.80 schema:affiliation https://www.grid.ac/institutes/grid.439102.d
172 schema:familyName Carlton
173 schema:givenName Timothy M.
174 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07570154354.80
175 rdf:type schema:Person
176 sg:pub.10.1007/s00253-005-0300-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027756420
177 https://doi.org/10.1007/s00253-005-0300-7
178 rdf:type schema:CreativeWork
179 sg:pub.10.1007/s003840050181 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018960758
180 https://doi.org/10.1007/s003840050181
181 rdf:type schema:CreativeWork
182 sg:pub.10.1007/s10620-015-4007-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1015197824
183 https://doi.org/10.1007/s10620-015-4007-z
184 rdf:type schema:CreativeWork
185 sg:pub.10.1007/s10875-009-9323-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043771900
186 https://doi.org/10.1007/s10875-009-9323-7
187 rdf:type schema:CreativeWork
188 sg:pub.10.1023/a:1005554900286 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026513664
189 https://doi.org/10.1023/a:1005554900286
190 rdf:type schema:CreativeWork
191 sg:pub.10.1038/mi.2009.116 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001891413
192 https://doi.org/10.1038/mi.2009.116
193 rdf:type schema:CreativeWork
194 sg:pub.10.1038/mi.2012.4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039750426
195 https://doi.org/10.1038/mi.2012.4
196 rdf:type schema:CreativeWork
197 sg:pub.10.1038/nm.3462 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004168882
198 https://doi.org/10.1038/nm.3462
199 rdf:type schema:CreativeWork
200 sg:pub.10.1111/j.1572-0241.2002.05914.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1007520375
201 https://doi.org/10.1111/j.1572-0241.2002.05914.x
202 rdf:type schema:CreativeWork
203 https://doi.org/10.1016/j.cgh.2015.10.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026803848
204 rdf:type schema:CreativeWork
205 https://doi.org/10.1016/j.jcmgh.2017.03.007 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084086244
206 rdf:type schema:CreativeWork
207 https://doi.org/10.1016/j.jim.2017.03.023 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084528572
208 rdf:type schema:CreativeWork
209 https://doi.org/10.1016/j.pathophys.2014.05.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002304542
210 rdf:type schema:CreativeWork
211 https://doi.org/10.1016/s0016-5085(99)70551-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051709830
212 rdf:type schema:CreativeWork
213 https://doi.org/10.1021/ja3061276 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055852951
214 rdf:type schema:CreativeWork
215 https://doi.org/10.1053/j.gastro.2011.08.032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036485440
216 rdf:type schema:CreativeWork
217 https://doi.org/10.1053/j.gastro.2014.03.049 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022952212
218 rdf:type schema:CreativeWork
219 https://doi.org/10.1053/j.gastro.2015.07.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023481453
220 rdf:type schema:CreativeWork
221 https://doi.org/10.1056/nejmct1209614 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053524613
222 rdf:type schema:CreativeWork
223 https://doi.org/10.1093/ecco-jcc/jjw026 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059495253
224 rdf:type schema:CreativeWork
225 https://doi.org/10.1093/ecco-jcc/jjw036 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059495261
226 rdf:type schema:CreativeWork
227 https://doi.org/10.1093/ecco-jcc/jjw053 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059495273
228 rdf:type schema:CreativeWork
229 https://doi.org/10.1093/protein/gzu011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029398507
230 rdf:type schema:CreativeWork
231 https://doi.org/10.1097/mib.0b013e3182a11958 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005155636
232 rdf:type schema:CreativeWork
233 https://doi.org/10.1136/gut.2004.047092 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005443029
234 rdf:type schema:CreativeWork
235 https://doi.org/10.1146/annurev-biochem-063011-092449 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022495591
236 rdf:type schema:CreativeWork
237 https://doi.org/10.1155/2012/718617 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009458252
238 rdf:type schema:CreativeWork
239 https://doi.org/10.1177/1756283x15576462 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064076555
240 rdf:type schema:CreativeWork
241 https://doi.org/10.1371/journal.pone.0028218 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003321057
242 rdf:type schema:CreativeWork
243 https://doi.org/10.3389/fimmu.2017.00867 schema:sameAs https://app.dimensions.ai/details/publication/pub.1090931878
244 rdf:type schema:CreativeWork
245 https://doi.org/10.3748/wjg.v22.i42.9300 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071374145
246 rdf:type schema:CreativeWork
247 https://doi.org/10.4161/mabs.12304 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072305518
248 rdf:type schema:CreativeWork
249 https://www.grid.ac/institutes/grid.10306.34 schema:alternateName Wellcome Sanger Institute
250 schema:name Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA, Hinxton, UK
251 rdf:type schema:Organization
252 https://www.grid.ac/institutes/grid.418195.0 schema:alternateName Babraham Institute
253 schema:name RxCelerate Ltd. Babraham Research Campus, CB22 3AT, Cambridge, UK
254 rdf:type schema:Organization
255 https://www.grid.ac/institutes/grid.439102.d schema:alternateName VHsquared (United Kingdom)
256 schema:name VHsquared Ltd., 1 Lower Court, Copley Hill, Cambridge Road, Babraham, CB22 3GN, Cambridge, UK
257 rdf:type schema:Organization
258 https://www.grid.ac/institutes/grid.4868.2 schema:alternateName Queen Mary University of London
259 schema:name Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, E1 2AT, London, UK
260 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...