PMC:7228307 / 38558-40048 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7228307","sourcedb":"PMC","sourceid":"7228307","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7228307","text":"The nature of the IgG isotype\nDifferent capabilities for the recruitment and activation of the different immune effector functions are naturally found in the Fc regions of the human IgG subclasses. Thus, to achieve a desired MOA, the different IgG subclasses are important starting points for the selection and engineering of the optimal mAb Fc. IgG1 is, in many ways, a proinflammatory or “effector‐active” subclass, as it can initiate the complement cascade and is a “universal” FcγR ligand.74 Notwithstanding it is also a ligand for the inhibitory FcγRIIb, IgG1 elicits proinflammatory responses through all activating‐type FcγRs, including ADCC, ADCP and cytokine release.\nBecause of their more restricted FcγR‐binding profile, IgG2 and IgG4 have offered some choice in potentially avoiding FcR effector function without the need for Fc engineering. They have been used as the backbone for therapeutic mAbs either because recruitment of patients’ effector functions was unlikely to be necessary for the primary MOA of the mAb or is possibly detrimental to the desired therapeutic effect.75 However, the use of these unmodified “inert” subclasses is not without consequences and underscores the need for Fc engineering to modify FcγR interactions—See the “Attenuating and ablating FcγR related functions of IgG” section.\nThus, the choice of IgG subclass for therapeutic mAb engineering is an important first step for engineering of novel mAbs of improved specificity, potency and safety.","divisions":[{"label":"title","span":{"begin":0,"end":29}},{"label":"p","span":{"begin":30,"end":676}},{"label":"p","span":{"begin":677,"end":1323}}],"tracks":[{"project":"LitCovid-PubTator","denotations":[{"id":"645","span":{"begin":551,"end":558},"obj":"Gene"},{"id":"646","span":{"begin":481,"end":485},"obj":"Gene"},{"id":"647","span":{"begin":176,"end":181},"obj":"Species"},{"id":"652","span":{"begin":710,"end":714},"obj":"Gene"},{"id":"653","span":{"begin":1284,"end":1288},"obj":"Gene"},{"id":"654","span":{"begin":1232,"end":1236},"obj":"Gene"},{"id":"655","span":{"begin":941,"end":949},"obj":"Species"}],"attributes":[{"id":"A645","pred":"tao:has_database_id","subj":"645","obj":"Gene:2213"},{"id":"A646","pred":"tao:has_database_id","subj":"646","obj":"Gene:2213"},{"id":"A647","pred":"tao:has_database_id","subj":"647","obj":"Tax:9606"},{"id":"A652","pred":"tao:has_database_id","subj":"652","obj":"Gene:2213"},{"id":"A653","pred":"tao:has_database_id","subj":"653","obj":"Gene:2213"},{"id":"A654","pred":"tao:has_database_id","subj":"654","obj":"Gene:2213"},{"id":"A655","pred":"tao:has_database_id","subj":"655","obj":"Tax:9606"},{"subj":"645","pred":"source","obj":"LitCovid-PubTator"},{"subj":"646","pred":"source","obj":"LitCovid-PubTator"},{"subj":"647","pred":"source","obj":"LitCovid-PubTator"},{"subj":"652","pred":"source","obj":"LitCovid-PubTator"},{"subj":"653","pred":"source","obj":"LitCovid-PubTator"},{"subj":"654","pred":"source","obj":"LitCovid-PubTator"},{"subj":"655","pred":"source","obj":"LitCovid-PubTator"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}]},{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T343","span":{"begin":18,"end":21},"obj":"Body_part"},{"id":"T344","span":{"begin":182,"end":185},"obj":"Body_part"},{"id":"T345","span":{"begin":244,"end":247},"obj":"Body_part"},{"id":"T346","span":{"begin":659,"end":667},"obj":"Body_part"},{"id":"T347","span":{"begin":881,"end":889},"obj":"Body_part"},{"id":"T348","span":{"begin":1310,"end":1313},"obj":"Body_part"},{"id":"T349","span":{"begin":1344,"end":1347},"obj":"Body_part"}],"attributes":[{"id":"A343","pred":"fma_id","subj":"T343","obj":"http://purl.org/sig/ont/fma/fma62872"},{"id":"A344","pred":"fma_id","subj":"T344","obj":"http://purl.org/sig/ont/fma/fma62872"},{"id":"A345","pred":"fma_id","subj":"T345","obj":"http://purl.org/sig/ont/fma/fma62872"},{"id":"A346","pred":"fma_id","subj":"T346","obj":"http://purl.org/sig/ont/fma/fma84050"},{"id":"A347","pred":"fma_id","subj":"T347","obj":"http://purl.org/sig/ont/fma/fma13478"},{"id":"A348","pred":"fma_id","subj":"T348","obj":"http://purl.org/sig/ont/fma/fma62872"},{"id":"A349","pred":"fma_id","subj":"T349","obj":"http://purl.org/sig/ont/fma/fma62872"},{"subj":"T343","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T344","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T345","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T346","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T347","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T348","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T349","pred":"source","obj":"LitCovid-PD-FMA-UBERON"}]},{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T57","span":{"begin":225,"end":228},"obj":"Disease"},{"id":"T58","span":{"begin":644,"end":648},"obj":"Disease"},{"id":"T59","span":{"begin":650,"end":654},"obj":"Disease"},{"id":"T60","span":{"begin":1015,"end":1018},"obj":"Disease"}],"attributes":[{"id":"A57","pred":"mondo_id","subj":"T57","obj":"http://purl.obolibrary.org/obo/MONDO_0016702"},{"id":"A58","pred":"mondo_id","subj":"T58","obj":"http://purl.obolibrary.org/obo/MONDO_0008734"},{"id":"A59","pred":"mondo_id","subj":"T59","obj":"http://purl.obolibrary.org/obo/MONDO_0022697"},{"id":"A60","pred":"mondo_id","subj":"T60","obj":"http://purl.obolibrary.org/obo/MONDO_0016702"},{"subj":"T57","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T58","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T59","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T60","pred":"source","obj":"LitCovid-PD-MONDO"}]},{"project":"LitCovid-PD-CLO","denotations":[{"id":"T697","span":{"begin":77,"end":87},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T698","span":{"begin":158,"end":160},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T699","span":{"begin":176,"end":185},"obj":"http://purl.obolibrary.org/obo/CLO_0053695"},{"id":"T700","span":{"begin":215,"end":216},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T701","span":{"begin":342,"end":344},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T702","span":{"begin":369,"end":370},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T703","span":{"begin":400,"end":406},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T704","span":{"begin":467,"end":468},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T705","span":{"begin":481,"end":483},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T706","span":{"begin":523,"end":524},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T707","span":{"begin":551,"end":553},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T708","span":{"begin":611,"end":621},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T709","span":{"begin":627,"end":629},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T710","span":{"begin":630,"end":632},"obj":"http://purl.obolibrary.org/obo/CLO_0008882"},{"id":"T711","span":{"begin":710,"end":712},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T712","span":{"begin":838,"end":840},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T713","span":{"begin":1207,"end":1209},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T714","span":{"begin":1232,"end":1234},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T715","span":{"begin":1284,"end":1286},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"}],"attributes":[{"subj":"T697","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T698","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T699","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T700","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T701","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T702","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T703","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T704","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T705","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T706","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T707","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T708","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T709","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T710","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T711","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T712","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T713","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T714","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T715","pred":"source","obj":"LitCovid-PD-CLO"}]},{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T205","span":{"begin":112,"end":120},"obj":"Chemical"},{"id":"T206","span":{"begin":391,"end":399},"obj":"Chemical"},{"id":"T207","span":{"begin":486,"end":492},"obj":"Chemical"},{"id":"T208","span":{"begin":525,"end":531},"obj":"Chemical"},{"id":"T209","span":{"begin":799,"end":807},"obj":"Chemical"},{"id":"T210","span":{"begin":951,"end":959},"obj":"Chemical"}],"attributes":[{"id":"A205","pred":"chebi_id","subj":"T205","obj":"http://purl.obolibrary.org/obo/CHEBI_35224"},{"id":"A206","pred":"chebi_id","subj":"T206","obj":"http://purl.obolibrary.org/obo/CHEBI_35224"},{"id":"A207","pred":"chebi_id","subj":"T207","obj":"http://purl.obolibrary.org/obo/CHEBI_52214"},{"id":"A208","pred":"chebi_id","subj":"T208","obj":"http://purl.obolibrary.org/obo/CHEBI_52214"},{"id":"A209","pred":"chebi_id","subj":"T209","obj":"http://purl.obolibrary.org/obo/CHEBI_35224"},{"id":"A210","pred":"chebi_id","subj":"T210","obj":"http://purl.obolibrary.org/obo/CHEBI_35224"},{"subj":"T205","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T206","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T207","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T208","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T209","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T210","pred":"source","obj":"LitCovid-PD-CHEBI"}]},{"project":"LitCovid-sample-PD-IDO","denotations":[{"id":"T199","span":{"begin":121,"end":130},"obj":"http://purl.obolibrary.org/obo/BFO_0000034"},{"id":"T200","span":{"begin":808,"end":816},"obj":"http://purl.obolibrary.org/obo/BFO_0000034"},{"id":"T201","span":{"begin":960,"end":969},"obj":"http://purl.obolibrary.org/obo/BFO_0000034"},{"id":"T202","span":{"begin":1297,"end":1306},"obj":"http://purl.obolibrary.org/obo/BFO_0000034"}],"attributes":[{"subj":"T199","pred":"source","obj":"LitCovid-sample-PD-IDO"},{"subj":"T200","pred":"source","obj":"LitCovid-sample-PD-IDO"},{"subj":"T201","pred":"source","obj":"LitCovid-sample-PD-IDO"},{"subj":"T202","pred":"source","obj":"LitCovid-sample-PD-IDO"}]},{"project":"LitCovid-sample-Pubtator","denotations":[{"id":"645","span":{"begin":551,"end":558},"obj":"Gene"},{"id":"646","span":{"begin":481,"end":485},"obj":"Gene"},{"id":"647","span":{"begin":176,"end":181},"obj":"Species"},{"id":"652","span":{"begin":710,"end":714},"obj":"Gene"},{"id":"653","span":{"begin":1284,"end":1288},"obj":"Gene"},{"id":"654","span":{"begin":1232,"end":1236},"obj":"Gene"},{"id":"655","span":{"begin":941,"end":949},"obj":"Species"},{"id":"979","span":{"begin":1284,"end":1288},"obj":"Gene"}],"attributes":[{"id":"A645","pred":"pubann:denotes","subj":"645","obj":"Gene:2213"},{"id":"A652","pred":"pubann:denotes","subj":"652","obj":"Gene:2213"},{"id":"A653","pred":"pubann:denotes","subj":"653","obj":"Gene:2213"},{"id":"A655","pred":"pubann:denotes","subj":"655","obj":"Tax:9606"},{"id":"A646","pred":"pubann:denotes","subj":"646","obj":"Gene:2213"},{"id":"A647","pred":"pubann:denotes","subj":"647","obj":"Tax:9606"},{"id":"A979","pred":"pubann:denotes","subj":"979","obj":"Gene:2213"},{"id":"A654","pred":"pubann:denotes","subj":"654","obj":"Gene:2213"},{"subj":"645","pred":"source","obj":"LitCovid-sample-Pubtator"},{"subj":"646","pred":"source","obj":"LitCovid-sample-Pubtator"},{"subj":"647","pred":"source","obj":"LitCovid-sample-Pubtator"},{"subj":"652","pred":"source","obj":"LitCovid-sample-Pubtator"},{"subj":"653","pred":"source","obj":"LitCovid-sample-Pubtator"},{"subj":"654","pred":"source","obj":"LitCovid-sample-Pubtator"},{"subj":"655","pred":"source","obj":"LitCovid-sample-Pubtator"},{"subj":"979","pred":"source","obj":"LitCovid-sample-Pubtator"}]},{"project":"LitCovid-sample-PD-NCBITaxon","denotations":[{"id":"T41","span":{"begin":176,"end":181},"obj":"Species"}],"attributes":[{"id":"A41","pred":"ncbi_taxonomy_id","subj":"T41","obj":"NCBItxid:9606"},{"subj":"T41","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"}],"namespaces":[{"prefix":"NCBItxid","uri":"http://purl.bioontology.org/ontology/NCBITAXON/"}]},{"project":"LitCovid-sample-sentences","denotations":[{"id":"T218","span":{"begin":0,"end":29},"obj":"Sentence"},{"id":"T219","span":{"begin":30,"end":197},"obj":"Sentence"},{"id":"T220","span":{"begin":198,"end":345},"obj":"Sentence"},{"id":"T221","span":{"begin":346,"end":676},"obj":"Sentence"},{"id":"T222","span":{"begin":677,"end":853},"obj":"Sentence"},{"id":"T223","span":{"begin":854,"end":1323},"obj":"Sentence"},{"id":"T224","span":{"begin":1324,"end":1490},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T218","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T219","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T220","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T221","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T222","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T223","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T224","pred":"source","obj":"LitCovid-sample-sentences"}]},{"project":"LitCovid-sample-PD-FMA","denotations":[{"id":"T342","span":{"begin":18,"end":21},"obj":"Body_part"},{"id":"T343","span":{"begin":182,"end":185},"obj":"Body_part"},{"id":"T344","span":{"begin":244,"end":247},"obj":"Body_part"},{"id":"T345","span":{"begin":659,"end":667},"obj":"Body_part"},{"id":"T346","span":{"begin":881,"end":889},"obj":"Body_part"},{"id":"T347","span":{"begin":1310,"end":1313},"obj":"Body_part"},{"id":"T348","span":{"begin":1344,"end":1347},"obj":"Body_part"}],"attributes":[{"id":"A346","pred":"fma_id","subj":"T346","obj":"http://purl.org/sig/ont/fma/fma13478"},{"id":"A343","pred":"fma_id","subj":"T343","obj":"http://purl.org/sig/ont/fma/fma62872"},{"id":"A344","pred":"fma_id","subj":"T344","obj":"http://purl.org/sig/ont/fma/fma62872"},{"id":"A345","pred":"fma_id","subj":"T345","obj":"http://purl.org/sig/ont/fma/fma84050"},{"id":"A347","pred":"fma_id","subj":"T347","obj":"http://purl.org/sig/ont/fma/fma62872"},{"id":"A342","pred":"fma_id","subj":"T342","obj":"http://purl.org/sig/ont/fma/fma62872"},{"id":"A348","pred":"fma_id","subj":"T348","obj":"http://purl.org/sig/ont/fma/fma62872"},{"subj":"T342","pred":"source","obj":"LitCovid-sample-PD-FMA"},{"subj":"T343","pred":"source","obj":"LitCovid-sample-PD-FMA"},{"subj":"T344","pred":"source","obj":"LitCovid-sample-PD-FMA"},{"subj":"T345","pred":"source","obj":"LitCovid-sample-PD-FMA"},{"subj":"T346","pred":"source","obj":"LitCovid-sample-PD-FMA"},{"subj":"T347","pred":"source","obj":"LitCovid-sample-PD-FMA"},{"subj":"T348","pred":"source","obj":"LitCovid-sample-PD-FMA"}]},{"project":"LitCovid-sample-PD-GO-BP-0","denotations":[{"id":"T94","span":{"begin":441,"end":459},"obj":"http://purl.obolibrary.org/obo/GO_0006956"},{"id":"T95","span":{"begin":644,"end":648},"obj":"http://purl.obolibrary.org/obo/GO_0001788"}],"attributes":[{"subj":"T94","pred":"source","obj":"LitCovid-sample-PD-GO-BP-0"},{"subj":"T95","pred":"source","obj":"LitCovid-sample-PD-GO-BP-0"}]},{"project":"LitCovid-sample-GO-BP","denotations":[{"id":"T95","span":{"begin":441,"end":459},"obj":"http://purl.obolibrary.org/obo/GO_0006956"},{"id":"T96","span":{"begin":644,"end":648},"obj":"http://purl.obolibrary.org/obo/GO_0001788"}],"attributes":[{"subj":"T95","pred":"source","obj":"LitCovid-sample-GO-BP"},{"subj":"T96","pred":"source","obj":"LitCovid-sample-GO-BP"}]},{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T95","span":{"begin":441,"end":459},"obj":"http://purl.obolibrary.org/obo/GO_0006956"},{"id":"T96","span":{"begin":644,"end":648},"obj":"http://purl.obolibrary.org/obo/GO_0001788"}],"attributes":[{"subj":"T95","pred":"source","obj":"LitCovid-PD-GO-BP"},{"subj":"T96","pred":"source","obj":"LitCovid-PD-GO-BP"}]},{"project":"LitCovid-sentences","denotations":[{"id":"T218","span":{"begin":0,"end":29},"obj":"Sentence"},{"id":"T219","span":{"begin":30,"end":197},"obj":"Sentence"},{"id":"T220","span":{"begin":198,"end":345},"obj":"Sentence"},{"id":"T221","span":{"begin":346,"end":676},"obj":"Sentence"},{"id":"T222","span":{"begin":677,"end":853},"obj":"Sentence"},{"id":"T223","span":{"begin":854,"end":1323},"obj":"Sentence"},{"id":"T224","span":{"begin":1324,"end":1490},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T218","pred":"source","obj":"LitCovid-sentences"},{"subj":"T219","pred":"source","obj":"LitCovid-sentences"},{"subj":"T220","pred":"source","obj":"LitCovid-sentences"},{"subj":"T221","pred":"source","obj":"LitCovid-sentences"},{"subj":"T222","pred":"source","obj":"LitCovid-sentences"},{"subj":"T223","pred":"source","obj":"LitCovid-sentences"},{"subj":"T224","pred":"source","obj":"LitCovid-sentences"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"LitCovid-PubTator","color":"#93ecc2","default":true},{"id":"LitCovid-PD-FMA-UBERON","color":"#eca893"},{"id":"LitCovid-PD-MONDO","color":"#9397ec"},{"id":"LitCovid-PD-CLO","color":"#b1ec93"},{"id":"LitCovid-PD-CHEBI","color":"#ec93cb"},{"id":"LitCovid-sample-PD-IDO","color":"#93e5ec"},{"id":"LitCovid-sample-Pubtator","color":"#ecd993"},{"id":"LitCovid-sample-PD-NCBITaxon","color":"#bf93ec"},{"id":"LitCovid-sample-sentences","color":"#93eca4"},{"id":"LitCovid-sample-PD-FMA","color":"#ec939b"},{"id":"LitCovid-sample-PD-GO-BP-0","color":"#93b5ec"},{"id":"LitCovid-sample-GO-BP","color":"#cfec93"},{"id":"LitCovid-PD-GO-BP","color":"#ec93e9"},{"id":"LitCovid-sentences","color":"#93ecd5"}]}]}}