{"id":"https://openalex.org/W4288068338","doi":"https://doi.org/10.3389/fimmu.2022.915412","title":"Immunogenicity Risk Assessment of Spontaneously Occurring Therapeutic Monoclonal Antibody Aggregates","display_name":"Immunogenicity Risk Assessment of Spontaneously Occurring Therapeutic Monoclonal Antibody Aggregates","publication_year":2022,"publication_date":"2022-07-27","ids":{"openalex":"https://openalex.org/W4288068338","doi":"https://doi.org/10.3389/fimmu.2022.915412","pmid":"https://pubmed.ncbi.nlm.nih.gov/35967308","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/9364768"},"language":"en","primary_location":{"id":"doi:10.3389/fimmu.2022.915412","doi":"https://doi.org/10.3389/fimmu.2022.915412","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2022.915412","pdf_url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.915412/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.915412/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5113547593","display_name":"Michael D. Swanson","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Michael D. Swanson","raw_affiliation_strings":["Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, United States","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052219745","display_name":"Shantel Rios","orcid":"https://orcid.org/0009-0004-4809-0567","observed_orcids":["https://orcid.org/0009-0004-4809-0567"]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shantel Rios","raw_affiliation_strings":["Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, United States","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Sarita Mittal","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sarita Mittal","raw_affiliation_strings":["Analytical R&D, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Analytical R&D, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, United States","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062623763","display_name":"George Soder","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"George Soder","raw_affiliation_strings":["Analytical R&D, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Analytical R&D, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, United States","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5104667324","display_name":"Vibha Jawa","orcid":"https://orcid.org/0000-0001-7019-729X","observed_orcids":["https://orcid.org/0000-0001-7019-729X","https://orcid.org/0000-0002-6463-4729"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Vibha Jawa","raw_affiliation_strings":["Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, NJ, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, NJ, United States","institution_ids":["https://openalex.org/I4210091812"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5113547593"],"corresponding_institution_ids":["https://openalex.org/I1285764155"],"apc_list":{"value":2950,"currency":"USD","value_usd":2950},"apc_paid":{"value":2950,"currency":"USD","value_usd":2950},"fwci":1.6313,"has_fulltext":true,"cited_by_count":34,"citation_normalized_percentile":{"value":0.8411421,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":95,"max":100},"biblio":{"volume":"13","issue":null,"first_page":"915412","last_page":"915412"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11124","display_name":"Protein purification and stability","score":0.5336999893188477,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11124","display_name":"Protein purification and stability","score":0.5336999893188477,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12255","display_name":"Biosimilars and Bioanalytical Methods","score":0.42329999804496765,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.030300000682473183,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/therapeutic-monoclonal-antibodies","display_name":"therapeutic monoclonal antibodies","score":0.8299999833106995},{"id":"https://openalex.org/keywords/protein-aggregation","display_name":"protein aggregation","score":0.7829999923706055},{"id":"https://openalex.org/keywords/immunogenicity-risk-assessment","display_name":"immunogenicity risk assessment","score":0.8970000147819519},{"id":"https://openalex.org/keywords/spontaneous-aggregation","display_name":"spontaneous aggregation","score":0.5839999914169312},{"id":"https://openalex.org/keywords/innate-immune-response","display_name":"innate immune response","score":0.6660000085830688},{"id":"https://openalex.org/keywords/peripheral-blood-mononuclear-cells","display_name":"peripheral blood mononuclear cells","score":0.9259999990463257},{"id":"https://openalex.org/keywords/cytokine-and-chemokine-production","display_name":"cytokine and chemokine production","score":0.9240000247955322}],"concepts":[{"id":"https://openalex.org/C2780868878","wikidata":"https://www.wikidata.org/wiki/Q1660197","display_name":"Immunogenicity","level":3,"score":0.9505534172058105},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.7188423275947571},{"id":"https://openalex.org/C137061746","wikidata":"https://www.wikidata.org/wiki/Q736033","display_name":"Peripheral blood mononuclear cell","level":3,"score":0.6477329730987549},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.5508506298065186},{"id":"https://openalex.org/C13373296","wikidata":"https://www.wikidata.org/wiki/Q421866","display_name":"Chemokine","level":3,"score":0.513009250164032},{"id":"https://openalex.org/C2776156784","wikidata":"https://www.wikidata.org/wiki/Q3491954","display_name":"Humanized mouse","level":3,"score":0.5127028226852417},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.5105482339859009},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.5017590522766113},{"id":"https://openalex.org/C2778690821","wikidata":"https://www.wikidata.org/wiki/Q212354","display_name":"Cytokine","level":2,"score":0.466336727142334},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4243714511394501},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.3533499836921692},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.32356545329093933},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.07350537180900574}],"mesh":[{"descriptor_ui":"D000911","descriptor_name":"Antibodies, Monoclonal","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007113","descriptor_name":"Immunity, Innate","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007963","descriptor_name":"Leukocytes, Mononuclear","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016207","descriptor_name":"Cytokines","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018570","descriptor_name":"Risk Assessment","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.3389/fimmu.2022.915412","doi":"https://doi.org/10.3389/fimmu.2022.915412","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2022.915412","pdf_url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.915412/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:9364768","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9364768","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Front Immunol","raw_type":"Text"},{"id":"pmid:35967308","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/35967308","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in immunology","raw_type":"Journal Article"},{"id":"pmh:oai:doaj.org/article:b2b14f47334e45659240aba38a26d4f7","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/b2b14f47334e45659240aba38a26d4f7","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Immunology, Vol 13 (2022)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fimmu.2022.915412","doi":"https://doi.org/10.3389/fimmu.2022.915412","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2022.915412","pdf_url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.915412/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9537000060081482}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4288068338.pdf","grobid_xml":"https://content.openalex.org/works/W4288068338.grobid-xml"},"referenced_works_count":41,"referenced_works":["https://openalex.org/W1264777543","https://openalex.org/W1673822629","https://openalex.org/W1783480860","https://openalex.org/W1943771969","https://openalex.org/W1968287902","https://openalex.org/W1970238011","https://openalex.org/W1973555453","https://openalex.org/W1993511309","https://openalex.org/W1999596528","https://openalex.org/W2011684044","https://openalex.org/W2018922312","https://openalex.org/W2019322677","https://openalex.org/W2019714972","https://openalex.org/W2030450209","https://openalex.org/W2031541912","https://openalex.org/W2048087821","https://openalex.org/W2061357129","https://openalex.org/W2067197313","https://openalex.org/W2129365134","https://openalex.org/W2161348982","https://openalex.org/W2319662570","https://openalex.org/W2336102284","https://openalex.org/W2433865296","https://openalex.org/W2481068577","https://openalex.org/W2558463870","https://openalex.org/W2587046531","https://openalex.org/W2593579259","https://openalex.org/W2785550499","https://openalex.org/W2795673785","https://openalex.org/W2798152178","https://openalex.org/W2872728035","https://openalex.org/W2916454924","https://openalex.org/W2926267620","https://openalex.org/W2969605137","https://openalex.org/W2982493799","https://openalex.org/W2988872960","https://openalex.org/W2988978365","https://openalex.org/W3016857155","https://openalex.org/W3034579403","https://openalex.org/W3199736194","https://openalex.org/W4221092793"],"related_works":["https://openalex.org/W2048087821","https://openalex.org/W4230605473","https://openalex.org/W1993511309","https://openalex.org/W7124753617","https://openalex.org/W1587991618","https://openalex.org/W2172770250","https://openalex.org/W3022004833","https://openalex.org/W2471997781","https://openalex.org/W4313384794","https://openalex.org/W7221098926"],"abstract_inverted_index":{"Aggregates":[0],"of":[1,36,47,173,184],"therapeutic":[2,69,95],"proteins":[3],"have":[4],"been":[5],"associated":[6],"with":[7,82,125],"increased":[8],"immunogenicity":[9,26,63,213],"in":[10,16,45,121,204,219],"pre-clinical":[11,218],"models":[12],"as":[13,15,130],"well":[14],"human":[17,225],"patients.":[18],"Recent":[19],"studies":[20],"to":[21,32,66,142,161,176],"understand":[22],"aggregates":[23,71,97,113],"and":[24,57,78,103,127,156,199],"their":[25,48],"risks":[27],"use":[28],"artificial":[29],"stress":[30,163],"methods":[31,39],"induce":[33],"high":[34,162],"levels":[35,183,191],"aggregation.":[37],"These":[38],"may":[40,200],"be":[41],"less":[42],"biologically":[43],"relevant":[44,190],"terms":[46],"quantity":[49],"than":[50,194],"those":[51,195],"that":[52],"occur":[53],"spontaneously":[54,67,93,143],"during":[55],"processing":[56],"storage.":[58],"Here":[59],"we":[60],"describe":[61],"the":[62,150,167],"risk":[64,203,214,221],"due":[65],"occurring":[68,94,112,144,187],"antibody":[70,185],"using":[72,216],"peripheral":[73],"blood":[74],"mononuclear":[75],"cells":[76],"(PBMC)":[77],"a":[79,83,122,131,170,217],"cell":[80,154],"line":[81,155],"reporter":[84],"gene":[85],"for":[86,118,133],"immune":[87,116,134,227],"activation:":[88],"THP-1":[89,151],"BLUE":[90,152],"NF\u03baB.":[91],"The":[92],"protein":[96],"were":[98,147],"obtained":[99],"from":[100,108,169],"process":[101,189],"intermediates":[102],"final":[104],"formulated":[105],"drug":[106],"substance":[107],"stability":[109],"retains.":[110],"Spontaneously":[111],"elicited":[114],"innate":[115],"responses":[117,141],"several":[119],"donors":[120,174],"PBMC":[123,157,168],"assay":[124],"cytokine":[126],"chemokine":[128],"production":[129],"readout":[132],"activation.":[135],"Meanwhile,":[136],"no":[137],"significant":[138],"adaptive":[139],"phase":[140],"aggregate":[145],"samples":[146],"detected.":[148],"While":[149],"NF\u03baB":[153],"assays":[158],"both":[159],"responded":[160,175],"induced":[164,196],"aggregates,":[165],"only":[166],"limited":[171],"subset":[172],"processing-induced":[177],"aggregates.":[178],"In":[179],"this":[180],"case":[181],"study,":[182],"aggregation":[186],"at":[188],"are":[192],"lower":[193,202],"by":[197],"stirring":[198],"pose":[201],"vivo":[205],".":[206],"Our":[207],"methodologies":[208],"can":[209],"further":[210],"inform":[211],"additional":[212],"assessments":[215],"vitro":[220],"assessment":[222],"approach":[223],"utilizing":[224],"derived":[226],"cells.":[228]},"counts_by_year":[{"year":2026,"cited_by_count":14},{"year":2025,"cited_by_count":8},{"year":2024,"cited_by_count":9},{"year":2023,"cited_by_count":3}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2022-07-28T00:00:00"}
