{"id":"https://openalex.org/W3083199593","doi":"https://doi.org/10.1158/1538-7445.am2020-584","title":"Abstract 584: TGN1412 induces dose and time dependent human cytokines in a humanized PBMC mouse model for cytokine release syndrome","display_name":"Abstract 584: TGN1412 induces dose and time dependent human cytokines in a humanized PBMC mouse model for cytokine release syndrome","publication_year":2020,"publication_date":"2020-08-15","ids":{"openalex":"https://openalex.org/W3083199593","doi":"https://doi.org/10.1158/1538-7445.am2020-584","mag":"3083199593"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2020-584","doi":"https://doi.org/10.1158/1538-7445.am2020-584","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2020-584","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Hongyuan Yang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210115256","display_name":"Jackson Laboratory","ror":"https://ror.org/021sy4w91","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210115256"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hongyuan Yang","raw_affiliation_strings":["1The Jackson Laboratory, Sacramento, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The Jackson Laboratory, Sacramento, CA;","institution_ids":["https://openalex.org/I4210115256"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029445167","display_name":"Jing Jiao","orcid":"https://orcid.org/0000-0002-0018-1353","observed_orcids":["https://orcid.org/0000-0002-0018-1353"]},"institutions":[{"id":"https://openalex.org/I4210115256","display_name":"Jackson Laboratory","ror":"https://ror.org/021sy4w91","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210115256"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jing Jiao","raw_affiliation_strings":["1The Jackson Laboratory, Sacramento, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The Jackson Laboratory, Sacramento, CA;","institution_ids":["https://openalex.org/I4210115256"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109449162","display_name":"Danying Cai","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210115256","display_name":"Jackson Laboratory","ror":"https://ror.org/021sy4w91","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210115256"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Danying Cai","raw_affiliation_strings":["1The Jackson Laboratory, Sacramento, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The Jackson Laboratory, Sacramento, CA;","institution_ids":["https://openalex.org/I4210115256"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079343876","display_name":"Mingshan Cheng","orcid":"https://orcid.org/0000-0002-4261-8007","observed_orcids":["https://orcid.org/0000-0002-4261-8007"]},"institutions":[{"id":"https://openalex.org/I4210115256","display_name":"Jackson Laboratory","ror":"https://ror.org/021sy4w91","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210115256"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mingshan Cheng","raw_affiliation_strings":["1The Jackson Laboratory, Sacramento, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The Jackson Laboratory, Sacramento, CA;","institution_ids":["https://openalex.org/I4210115256"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023032912","display_name":"Michael A. Brehm","orcid":"https://orcid.org/0000-0001-6813-3262","observed_orcids":["https://orcid.org/0000-0001-6813-3262"]},"institutions":[{"id":"https://openalex.org/I166722992","display_name":"University of Massachusetts Chan Medical School","ror":"https://ror.org/0464eyp60","country_code":"US","type":"education","lineage":["https://openalex.org/I166722992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael Brehm","raw_affiliation_strings":["2The University of Massachusetts Medical School, Worcester, MA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2The University of Massachusetts Medical School, Worcester, MA;","institution_ids":["https://openalex.org/I166722992"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025563484","display_name":"Dale Grainer","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I166722992","display_name":"University of Massachusetts Chan Medical School","ror":"https://ror.org/0464eyp60","country_code":"US","type":"education","lineage":["https://openalex.org/I166722992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dale Grainer","raw_affiliation_strings":["2The University of Massachusetts Medical School, Worcester, MA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2The University of Massachusetts Medical School, Worcester, MA;","institution_ids":["https://openalex.org/I166722992"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036394378","display_name":"Leonard D. Shultz","orcid":"https://orcid.org/0000-0002-4868-1031","observed_orcids":["https://orcid.org/0000-0002-4868-1031"]},"institutions":[{"id":"https://openalex.org/I4210115256","display_name":"Jackson Laboratory","ror":"https://ror.org/021sy4w91","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210115256"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Leonard Shultz","raw_affiliation_strings":["3The Jackson Laboratory, Bar Harbor, ME"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3The Jackson Laboratory, Bar Harbor, ME","institution_ids":["https://openalex.org/I4210115256"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5033226354","display_name":"James Keck","orcid":"https://orcid.org/0000-0002-6835-5671","observed_orcids":["https://orcid.org/0000-0002-6835-5671"]},"institutions":[{"id":"https://openalex.org/I4210115256","display_name":"Jackson Laboratory","ror":"https://ror.org/021sy4w91","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210115256"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"James Keck","raw_affiliation_strings":["1The Jackson Laboratory, Sacramento, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The Jackson Laboratory, Sacramento, CA;","institution_ids":["https://openalex.org/I4210115256"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"80","issue":"16_Supplement","first_page":"584","last_page":"584"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T14072","display_name":"Immunotoxicology and immune responses","score":0.5067999958992004,"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"}},"topics":[{"id":"https://openalex.org/T14072","display_name":"Immunotoxicology and immune responses","score":0.5067999958992004,"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.26420000195503235,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.08510000258684158,"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/tgn1412","display_name":"TGN1412","score":0.9570000171661377},{"id":"https://openalex.org/keywords/cytokine-release-syndrome","display_name":"cytokine release syndrome","score":0.9890000224113464},{"id":"https://openalex.org/keywords/humanized-mouse-model","display_name":"humanized mice","score":0.8270000219345093},{"id":"https://openalex.org/keywords/anti-cd28-monoclonal-antibody","display_name":"anti-CD28 monoclonal antibody","score":0.9200000166893005},{"id":"https://openalex.org/keywords/tnf-alpha","display_name":"TNF-\u03b1","score":0.6949999928474426},{"id":"https://openalex.org/keywords/interferon-gamma","display_name":"interferon-gamma","score":0.7590000033378601},{"id":"https://openalex.org/keywords/immune-checkpoint-inhibitors","display_name":"immune checkpoint inhibitors","score":0.7409999966621399},{"id":"https://openalex.org/keywords/bispecific-antibodies","display_name":"bispecific antibodies","score":0.9909999966621399},{"id":"https://openalex.org/keywords/preclinical-safety-evaluation","display_name":"preclinical safety","score":0.7149999737739563},{"id":"https://openalex.org/keywords/nsg-mice","display_name":"NSG mice","score":0.6859999895095825},{"id":"https://openalex.org/keywords/t-cell-depletion","display_name":"T cell depletion","score":0.531000018119812}],"concepts":[{"id":"https://openalex.org/C137061746","wikidata":"https://www.wikidata.org/wiki/Q736033","display_name":"Peripheral blood mononuclear cell","level":3,"score":0.6964494585990906},{"id":"https://openalex.org/C2778690821","wikidata":"https://www.wikidata.org/wiki/Q212354","display_name":"Cytokine","level":2,"score":0.689277172088623},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6626495718955994},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.6036940813064575},{"id":"https://openalex.org/C2780850621","wikidata":"https://www.wikidata.org/wiki/Q3961647","display_name":"Cytokine release syndrome","level":5,"score":0.5951780080795288},{"id":"https://openalex.org/C2776156784","wikidata":"https://www.wikidata.org/wiki/Q3491954","display_name":"Humanized mouse","level":3,"score":0.5699949860572815},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.5531246066093445},{"id":"https://openalex.org/C17991360","wikidata":"https://www.wikidata.org/wiki/Q21173843","display_name":"Tumor necrosis factor alpha","level":2,"score":0.5298464298248291},{"id":"https://openalex.org/C148125776","wikidata":"https://www.wikidata.org/wiki/Q1622348","display_name":"CD28","level":4,"score":0.4836481809616089},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.47070929408073425},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.4603220820426941},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.4397616982460022},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.43311068415641785},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4228877127170563},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.31186118721961975},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.2914921045303345},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.27507686614990234},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.201800137758255},{"id":"https://openalex.org/C3875195","wikidata":"https://www.wikidata.org/wiki/Q5099363","display_name":"Chimeric antigen receptor","level":4,"score":0.0528184175491333},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2020-584","doi":"https://doi.org/10.1158/1538-7445.am2020-584","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2020-584","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":1.0,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2941450171","https://openalex.org/W3047960095","https://openalex.org/W2293418118","https://openalex.org/W3081880721","https://openalex.org/W2954277586","https://openalex.org/W2947188179","https://openalex.org/W2005598333","https://openalex.org/W4409821305","https://openalex.org/W3030907933","https://openalex.org/W2955980644"],"abstract_inverted_index":{"Abstract":[0],"There":[1],"have":[2,89,264],"been":[3],"remarkable":[4],"progresses":[5],"in":[6,109,194,218,223,235,250,254,260,281,302,323,342,371],"the":[7,15,32,69,114,195,207,224,236,255,267,385,389],"development":[8],"of":[9,17,24,27,34,55,116,184,326,384,388],"immune":[10,18,84,332],"therapies":[11],"for":[12,78,140,171,313,377,392],"cancer.":[13],"However,":[14],"promise":[16],"therapy":[19],"comes":[20],"with":[21,137,146,200,240,299,337],"significant":[22,216,248],"challenges":[23],"a":[25,45,53,75,91,124,247,282,294,318,372],"variety":[26],"adverse":[28,42,296],"effects.":[29],"Due":[30],"to":[31,38,57,321],"lack":[33],"predictive":[35],"preclinical":[36],"model":[37,97,270,312,376],"evaluate":[39],"antibody":[40,49],"mediated":[41],"effects,":[43],"TGN1412,":[44],"humanized":[46,237,373],"anti-CD28":[47],"monoclonal":[48],"which":[50],"acts":[51],"as":[52,123,132],"superagonist":[54],"CD28":[56],"activate":[58],"T":[59],"cells,":[60],"unfortunately":[61],"caused":[62],"life-threatening":[63],"cytokine":[64,101,175,378],"release":[65,102,379],"syndrome":[66,380],"(CRS)":[67],"during":[68],"first-in-man":[70],"trial.":[71],"Therefore":[72],"there":[73],"is":[74],"critical":[76],"need":[77],"translational":[79],"protocols":[80],"that":[81,98,266,289,307],"could":[82,292],"predict":[83],"toxicity":[85],"more":[86],"accurately.":[87],"We":[88,177,263],"developed":[90,310],"sensitive":[92],"and":[93,153,166,174,180,191,206,246,284,335,366,399],"reproducible":[94],"PBMC-humanized":[95,272],"mouse":[96,269,311,375],"can":[99,274],"measure":[100],"induced":[103,278],"by":[104,279],"bispecifics":[105,336],"or":[106,128],"checkpoint":[107,333],"inhibitors":[108,334],"vivo.":[110],"In":[111],"this":[112,117],"study":[113],"utility":[115],"platform":[118],"was":[119,158,221,233,258],"demonstrated":[120,265],"using":[121,271],"TGN1412":[122,147,198,232,280,300,363],"model.":[125],"NSG\u2122":[126,238,273],"mice":[127,134,239],"derivative":[129],"strains":[130],"such":[131],"SGM3":[133],"were":[135],"engrafted":[136],"human":[138,185,328,369],"PBMCs":[139,241],"6":[141],"days":[142],"before":[143],"being":[144],"treated":[145],"at":[148,160,203,210,228],"different":[149,244],"concentrations":[150],"(0.2,":[151],"1.0":[152],"2":[154],"mg/kg).":[155],"Mouse":[156],"blood":[157,226,257],"collected":[159,227],"1,":[161],"2,":[162],"4,":[163],"6,":[164],"24":[165],"48":[167],"hours":[168],"post":[169,213,230],"dose":[170,179,283,365],"flow":[172],"cytometry":[173],"analysis.":[176],"observed":[178,222,259],"time":[181,285,367],"dependent":[182,286,368],"increase":[183],"IFN-\u03b3,":[186],"TNF\u03b1,":[187],"IL-2,":[188],"IL-4,":[189],"IL-6":[190],"IL-10":[192],"levels":[193],"serum":[196],"following":[197],"treatment":[199,301],"TNF\u03b1":[201],"peaking":[202,209],"1":[204],"h":[205,212],"others":[208],"2-4":[211],"dose.":[214],"A":[215],"decrease":[217,249],"hCD45+":[219,251],"cells":[220],"peripheral":[225,256],"6h":[229],"treatment.":[231],"tested":[234],"from":[242],"7":[243],"donors,":[245],"cell":[252],"population":[253],"all":[261],"donors.":[262],"novel":[268],"successfully":[275],"detect":[276],"CRS":[277,291,314],"manner,":[287],"suggesting":[288],"indeed":[290],"be":[293,317],"strong":[295],"effect":[297],"associated":[298],"human.":[303],"Our":[304],"data":[305],"supports":[306],"our":[308],"newly":[309],"assessment":[315],"may":[316],"valuable":[319],"tool":[320],"assess":[322],"vivo":[324],"safety":[325],"experimental":[327],"therapeutic":[329],"antibodies":[330],"including":[331],"better":[338],"reliability":[339],"than":[340],"an":[341],"vitro":[343],"assay.":[344],"Citation":[345],"Format:":[346],"Hongyuan":[347],"Yang,":[348],"Jing":[349],"Jiao,":[350],"Danying":[351],"Cai,":[352],"Mingshan":[353],"Cheng,":[354],"Michael":[355],"Brehm,":[356],"Dale":[357],"Grainer,":[358],"Leonard":[359],"Shultz,":[360],"James":[361],"Keck.":[362],"induces":[364],"cytokines":[370],"PBMC":[374],"[abstract].":[381],"In:":[382],"Proceedings":[383],"Annual":[386],"Meeting":[387],"American":[390],"Association":[391],"Cancer":[393,405],"Research":[394],"2020;":[395],"2020":[396],"Apr":[397],"27-28":[398],"Jun":[400],"22-24.":[401],"Philadelphia":[402],"(PA):":[403],"AACR;":[404],"Res":[406],"2020;80(16":[407],"Suppl):Abstract":[408],"nr":[409],"584.":[410]},"counts_by_year":[],"updated_date":"2026-10-14T16:39:01.820549","created_date":"2020-09-11T00:00:00"}