{"id":"https://openalex.org/W4308398374","doi":"https://doi.org/10.1136/jitc-2022-sitc2022.0410","title":"410 Priming of SynNotch CAR T cells via CNS-specific antigen allows spatial and temporal regulation of CAR expression, effective homing and persistence of T cells in the CNS, resulting in the complete eradication of aggresive glioblastoma","display_name":"410 Priming of SynNotch CAR T cells via CNS-specific antigen allows spatial and temporal regulation of CAR expression, effective homing and persistence of T cells in the CNS, resulting in the complete eradication of aggresive glioblastoma","publication_year":2022,"publication_date":"2022-11-01","ids":{"openalex":"https://openalex.org/W4308398374","doi":"https://doi.org/10.1136/jitc-2022-sitc2022.0410"},"language":"en","primary_location":{"id":"doi:10.1136/jitc-2022-sitc2022.0410","doi":"https://doi.org/10.1136/jitc-2022-sitc2022.0410","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2022-sitc2022.0410","pdf_url":"https://jitc.bmj.com/content/jitc/10/Suppl_2/A432.full.pdf","source":{"id":"https://openalex.org/S2754803477","display_name":"Journal for ImmunoTherapy of Cancer","issn_l":"2051-1426","issn":["2051-1426"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319945","host_organization_name":"BMJ","host_organization_lineage":["https://openalex.org/P4310319945"],"host_organization_lineage_names":["BMJ"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Regular and Young Investigator Award Abstracts","raw_type":"proceedings-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://jitc.bmj.com/content/jitc/10/Suppl_2/A432.full.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5048998314","display_name":"Payal B. Watchmaker","orcid":"https://orcid.org/0000-0002-0944-3890","observed_orcids":["https://orcid.org/0000-0002-0944-3890"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Payal Watchmaker","raw_affiliation_strings":["UCSF, San Francisco, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UCSF, San Francisco, CA, United States","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034967094","display_name":"Milos Simic","orcid":"https://orcid.org/0000-0002-1167-0857","observed_orcids":["https://orcid.org/0000-0002-1167-0857"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Milos Simic","raw_affiliation_strings":["UCSF, San Francisco, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UCSF, San Francisco, CA, United States","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009574522","display_name":"David Diebold","orcid":"https://orcid.org/0000-0002-6857-767X","observed_orcids":["https://orcid.org/0000-0002-6857-767X"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Diebold","raw_affiliation_strings":["UCSF, San Francisco, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UCSF, San Francisco, CA, United States","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054564812","display_name":"Psalm L. Pineo-Cavanaugh","orcid":"https://orcid.org/0000-0002-1521-1607","observed_orcids":["https://orcid.org/0000-0002-1521-1607"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Psalm Pineo-Cavanaugh","raw_affiliation_strings":["UCSF, San Francisco, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UCSF, San Francisco, CA, United States","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072474123","display_name":"Jason Duecker","orcid":"https://orcid.org/0000-0002-4978-0867","observed_orcids":["https://orcid.org/0000-0002-4978-0867"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jason Duecker","raw_affiliation_strings":["UCSF, San Francisco, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UCSF, San Francisco, CA, United States","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Wei Yu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wei Yu","raw_affiliation_strings":["UCSF, San Francisco, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UCSF, San Francisco, CA, United States","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006257775","display_name":"Wendell A. Lim","orcid":"https://orcid.org/0000-0003-4052-8056","observed_orcids":["https://orcid.org/0000-0003-4052-8056"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wendell Lim","raw_affiliation_strings":["UCSF, San Francisco, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UCSF, San Francisco, CA, United States","institution_ids":["https://openalex.org/I180670191"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5058793243","display_name":"Hideho Okada","orcid":"https://orcid.org/0000-0003-0076-9920","observed_orcids":["https://orcid.org/0000-0003-0076-9920"]},"institutions":[{"id":"https://openalex.org/I180670191","display_name":"University of California, San Francisco","ror":"https://ror.org/043mz5j54","country_code":"US","type":"education","lineage":["https://openalex.org/I180670191"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hideho Okada","raw_affiliation_strings":["UCSF, San Francisco, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UCSF, San Francisco, CA, United States","institution_ids":["https://openalex.org/I180670191"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I180670191"],"apc_list":{"value":2490,"currency":"USD","value_usd":2490},"apc_paid":{"value":2490,"currency":"USD","value_usd":2490},"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"A432","last_page":"A432"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11491","display_name":"CAR-T cell therapy research","score":0.9926999807357788,"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"}},"topics":[{"id":"https://openalex.org/T11491","display_name":"CAR-T cell therapy research","score":0.9926999807357788,"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/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.005100000184029341,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics (clinical)"},"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/T10580","display_name":"Immunotherapy and Immune Responses","score":0.00039999998989515007,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/car-t-cell-therapy","display_name":"CAR T-cell therapy","score":0.7360000014305115},{"id":"https://openalex.org/keywords/synthetic-notch-receptor","display_name":"synthetic Notch receptor","score":0.8199999928474426},{"id":"https://openalex.org/keywords/glioblastoma","display_name":"glioblastoma","score":0.9869999885559082},{"id":"https://openalex.org/keywords/epha2","display_name":"EphA2","score":0.800000011920929},{"id":"https://openalex.org/keywords/il13ralpha2","display_name":"IL13R\u03b12","score":0.9800000190734863},{"id":"https://openalex.org/keywords/t-cell-homing","display_name":"T cell homing","score":0.722000002861023},{"id":"https://openalex.org/keywords/t-cell-persistence","display_name":"T cell persistence","score":0.9660000205039978},{"id":"https://openalex.org/keywords/tumor-specific-antigens","display_name":"tumor-specific antigens","score":0.32100000977516174},{"id":"https://openalex.org/keywords/egfrviii","display_name":"EGFRvIII","score":0.8460000157356262},{"id":"https://openalex.org/keywords/glioma-associated-antigens","display_name":"glioma-associated antigens","score":0.5630000233650208},{"id":"https://openalex.org/keywords/brain-tumor-immunotherapy","display_name":"brain tumor immunotherapy","score":0.4350000023841858}],"concepts":[{"id":"https://openalex.org/C81444415","wikidata":"https://www.wikidata.org/wiki/Q7243535","display_name":"Priming (agriculture)","level":3,"score":0.8370850086212158},{"id":"https://openalex.org/C147483822","wikidata":"https://www.wikidata.org/wiki/Q103537","display_name":"Antigen","level":2,"score":0.6544244885444641},{"id":"https://openalex.org/C2778227246","wikidata":"https://www.wikidata.org/wiki/Q1365309","display_name":"Glioma","level":2,"score":0.5933932065963745},{"id":"https://openalex.org/C154317977","wikidata":"https://www.wikidata.org/wiki/Q376266","display_name":"Cytotoxic T cell","level":3,"score":0.514130175113678},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.492303729057312},{"id":"https://openalex.org/C3875195","wikidata":"https://www.wikidata.org/wiki/Q5099363","display_name":"Chimeric antigen receptor","level":4,"score":0.4298953711986542},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.41963425278663635},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.395274817943573},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.35574012994766235},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.34137192368507385},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.330584317445755},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.06278082728385925},{"id":"https://openalex.org/C100701293","wikidata":"https://www.wikidata.org/wiki/Q193838","display_name":"Germination","level":2,"score":0.0},{"id":"https://openalex.org/C59822182","wikidata":"https://www.wikidata.org/wiki/Q441","display_name":"Botany","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:10.1136/jitc-2022-sitc2022.0410","doi":"https://doi.org/10.1136/jitc-2022-sitc2022.0410","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2022-sitc2022.0410","pdf_url":"https://jitc.bmj.com/content/jitc/10/Suppl_2/A432.full.pdf","source":{"id":"https://openalex.org/S2754803477","display_name":"Journal for ImmunoTherapy of Cancer","issn_l":"2051-1426","issn":["2051-1426"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319945","host_organization_name":"BMJ","host_organization_lineage":["https://openalex.org/P4310319945"],"host_organization_lineage_names":["BMJ"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Regular and Young Investigator Award Abstracts","raw_type":"proceedings-article"}],"best_oa_location":{"id":"doi:10.1136/jitc-2022-sitc2022.0410","doi":"https://doi.org/10.1136/jitc-2022-sitc2022.0410","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2022-sitc2022.0410","pdf_url":"https://jitc.bmj.com/content/jitc/10/Suppl_2/A432.full.pdf","source":{"id":"https://openalex.org/S2754803477","display_name":"Journal for ImmunoTherapy of Cancer","issn_l":"2051-1426","issn":["2051-1426"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319945","host_organization_name":"BMJ","host_organization_lineage":["https://openalex.org/P4310319945"],"host_organization_lineage_names":["BMJ"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Regular and Young Investigator Award Abstracts","raw_type":"proceedings-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/W4308398374.pdf","grobid_xml":"https://content.openalex.org/works/W4308398374.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4309017210","https://openalex.org/W4404857465","https://openalex.org/W3113178349","https://openalex.org/W3157520262","https://openalex.org/W4388048274","https://openalex.org/W2987276631","https://openalex.org/W2900116999","https://openalex.org/W7154728646","https://openalex.org/W4281736359","https://openalex.org/W3120167422"],"abstract_inverted_index":{"Background":[0],"The":[1,301],"CAR":[2,79,141,185,245,273,298,342],"T":[3,142,238,265,288,299,311,335,352,391],"cell":[4,222,336],"therapies":[5],"have":[6,38,96,199],"failed":[7],"to":[8,179,240,359,371],"produce":[9],"long-term":[10],"remission":[11],"in":[12,20,47,101,133,233,303,393],"glioma":[13,361],"patients.":[14,362],"One":[15],"of":[16,23,31,59,116,163,183,243,264,282,309,350,385,387],"the":[17,21,29,48,55,60,102,134,138,155,164,176,184,192,207,214,237,269,283,325,339,347,357,373,378,388],"key":[18],"challenges":[19,162],"development":[22],"an":[24],"effective":[25],"CAR-T":[26],"therapy":[27,337],"is":[28],"absence":[30],"target":[32,43],"antigens":[33,45,174],"that":[34,225,246],"are":[35,364],"tumor-specific":[36,195],"and":[37,71,75,95,137,188,190,216,249,306,318,332,380],"homogenous":[39],"expression.":[40,111],"To":[41,158],"safely":[42],"glioblastoma-associated":[44],"(GAAs)":[46],"tumor":[49,107],"without":[50],"attacking":[51],"normal":[52],"tissue":[53],"expressing":[54],"same":[56],"GAAs":[57],"outside":[58],"brain,":[61],"we":[62,167,226],"adopted":[63],"a":[64,73,89,230,244,259,329,367],"novel":[65,334],"synthetic":[66],"Notch":[67],"(synNotch)":[68],"receptor":[69,94],"system":[70],"established":[72],"\u201cprime":[74],"kill\u201d":[76],"sequential":[77],"two-receptor":[78],"circuit.":[80],"We":[81,198,228,363],"used":[82,168],"glioblastoma-":[83],"(GBM)":[84],"specific":[85,215],"neoantigen":[86],"EGFRvIII":[87,110,123],"as":[88,175,204,206,375,377],"priming":[90,156,177,210,218,381],"signal":[91,178],"for":[92,194],"synNotch":[93,271],"reported":[97],"robust":[98,217],"antitumor":[99],"response":[100],"mice":[103,253,277],"bearing":[104,254],"intracerebral":[105,255],"PDX":[106,257],"with":[108,268,315,338,395],"heterogenous":[109],"However,":[112],"less":[113],"than":[114,294],"20%":[115],"adult":[117],"GBM":[118,147],"cases":[119],"express":[120],"EGFRvIII.":[121],"Furthermore,":[122,285],"expression":[124,182,242,384],"can":[125],"diminish":[126],"over":[127],"time":[128],"even":[129],"after":[130],"its":[131,316],"detection":[132],"primary":[135],"GBM,":[136],"EGFRvIII-synNotch":[139],"primed":[140],"cells":[143,148,239,266,289,312,353,392],"may":[144],"deplete":[145],"EGFRvIII-expressing":[146],"via":[149],"their":[150],"cytotoxic":[151],"effects,":[152],"thereby":[153],"losing":[154],"signal.":[157],"overcome":[159],"these":[160,286],"inherent":[161],"EGFRvIII-priming":[165],"strategy,":[166],"CNS":[169,340],"(Central":[170],"Nervous":[171],"System)":[172],"tissue-specific":[173,341],"drive":[180],"localized":[181],"against":[186],"EphA2":[187],"IL-13R\u03b12":[189,248],"bypassed":[191],"need":[193],"antigen.":[196],"Methods":[197],"found":[200],"BCAN":[201,235],"(also":[202],"known":[203],"Brevican)":[205],"most":[208],"promising":[209],"antigen":[211],"based":[212],"on":[213],"among":[219],"several":[220],"CNS-specific":[221],"surface":[223],"proteins":[224],"evaluated.":[227],"created":[229],"synNotch-CAR":[231,351],"circuit":[232],"which":[234],"primes":[236],"induce":[241],"recognizes":[247],"EphA2.":[250],"Results":[251],"When":[252],"GBM6":[256],"received":[258],"single":[260],"intravenous":[261],"(IV)":[262],"infusion":[263],"engineered":[267],"\u03b1-BCAN":[270],"\u03b1-EphA2/IL-13R\u03b12":[272],"(B-SYNC)":[274],"circuit,":[275],"all":[276],"(10/10)":[278],"demonstrated":[279],"complete":[280],"regression":[281],"tumor.":[284],"B-SYNC":[287,310,326,390],"were":[290,313],"significantly":[291],"more":[292],"efficacious":[293,331],"constitutively":[295],"expressed":[296],"EphA2/IL-13R\u03b12":[297],"cells.":[300],"enhanced":[302],"vivo":[304],"efficacy":[305],"superior":[307],"persistence":[308],"associated":[314],"tissue-resident":[317],"memory":[319],"stem-cell-like":[320],"phenotype.":[321],"Conclusions":[322],"Taken":[323],"together,":[324],"approach":[327],"represents":[328],"robustly":[330],"conceptually":[333],"activation.":[343],"This":[344],"also":[345],"enhances":[346],"translational":[348],"significance":[349],"by":[354],"widely":[355],"extending":[356],"eligibility":[358],"EGFRvIII-negative":[360],"currently":[365],"developing":[366],"phase":[368],"I":[369],"study":[370],"evaluate":[372],"safety":[374],"well":[376],"homing":[379],"status":[382],"(i.e.":[383],"CAR)":[386],"IV-infused":[389],"patients":[394],"GBM.":[396]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2022-11-11T00:00:00"}