{"id":"https://openalex.org/W4404064671","doi":"https://doi.org/10.1136/jitc-2024-sitc2024.0388","title":"388 Engineering co-stimulation into TCR-T cells via a CD8\u201341BB fusion receptor enhances efficacy and durability in preclinical models of heme and solid tumor malignancies","display_name":"388 Engineering co-stimulation into TCR-T cells via a CD8\u201341BB fusion receptor enhances efficacy and durability in preclinical models of heme and solid tumor malignancies","publication_year":2024,"publication_date":"2024-11-01","ids":{"openalex":"https://openalex.org/W4404064671","doi":"https://doi.org/10.1136/jitc-2024-sitc2024.0388"},"language":"en","primary_location":{"id":"doi:10.1136/jitc-2024-sitc2024.0388","doi":"https://doi.org/10.1136/jitc-2024-sitc2024.0388","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2024-sitc2024.0388","pdf_url":null,"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":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","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","is_traditional":false,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1136/jitc-2024-sitc2024.0388","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5053344913","display_name":"Aaron Prodeus","orcid":"https://orcid.org/0000-0002-0719-3891","observed_orcids":["https://orcid.org/0000-0002-0719-3891"]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Aaron Prodeus","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056115152","display_name":"Ivy Dutta","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ivy Dutta","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110207419","display_name":"Justin D. Oh","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Justin Oh","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083169377","display_name":"L. Le Cam","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Liz Cam","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062967629","display_name":"Allie Luther","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Allie Luther","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000443562","display_name":"Palak Sharma","orcid":"https://orcid.org/0000-0001-8870-9097","observed_orcids":["https://orcid.org/0000-0001-8870-9097","https://orcid.org/0000-0003-4504-2071","https://orcid.org/0009-0007-0403-9948"]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Palak Sharma","raw_affiliation_strings":["Intellia Therapeutics Inc., Watertown, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Watertown, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025202178","display_name":"Ishina Balwani","orcid":"https://orcid.org/0009-0000-7773-5222","observed_orcids":["https://orcid.org/0009-0000-7773-5222"]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ishina Balwani","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":null,"display_name":"James Peter","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"James Peter","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Ian Miller","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ian Miller","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5114524918","display_name":"Lekshmi Maya","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lekshmi Maya","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031090561","display_name":"Elena Stampouloglou","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Elena Stampouloglou","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":null,"display_name":"James Bowen","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"James Bowen","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075896421","display_name":"Dai Liu","orcid":"https://orcid.org/0000-0002-7479-2237","observed_orcids":["https://orcid.org/0000-0002-7479-2237"]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dai Liu","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022909911","display_name":"Eliana Ruggiero","orcid":"https://orcid.org/0000-0002-2954-8278","observed_orcids":["https://orcid.org/0000-0002-2954-8278"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Eliana Ruggiero","raw_affiliation_strings":["IRCCS San Raffaele Scientific Institute, Milan, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"IRCCS San Raffaele Scientific Institute, Milan, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074043746","display_name":"Chiara Bonini","orcid":"https://orcid.org/0000-0002-0772-1674","observed_orcids":["https://orcid.org/0000-0002-0772-1674"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Chiara Bonini","raw_affiliation_strings":["IRCCS San Raffaele Scientific Institute, Milan, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"IRCCS San Raffaele Scientific Institute, Milan, Italy","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5050867417","display_name":"Birgit C. Schultes","orcid":"https://orcid.org/0000-0002-2275-3383","observed_orcids":["https://orcid.org/0000-0002-2275-3383"]},"institutions":[{"id":"https://openalex.org/I4210131291","display_name":"Intellia Therapeutics (United States)","ror":"https://ror.org/03b368668","country_code":"US","type":"company","lineage":["https://openalex.org/I4210131291"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Birgit Schultes","raw_affiliation_strings":["Intellia Therapeutics Inc., Cambridge, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Intellia Therapeutics Inc., Cambridge, MA, USA","institution_ids":["https://openalex.org/I4210131291"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":2490,"currency":"USD","value_usd":2490},"apc_paid":{"value":2490,"currency":"USD","value_usd":2490},"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"A447","last_page":"A447"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11491","display_name":"CAR-T cell therapy research","score":0.9922000169754028,"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":0.9922000169754028,"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/T10580","display_name":"Immunotherapy and Immune Responses","score":0.004999999888241291,"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/T10031","display_name":"T-cell and B-cell Immunology","score":0.000699999975040555,"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/tcr-engineered-t-cells","display_name":"TCR-engineered T cells","score":0.7749999761581421},{"id":"https://openalex.org/keywords/costimulation","display_name":"costimulation","score":0.8650000095367432},{"id":"https://openalex.org/keywords/adoptive-immunotherapy","display_name":"adoptive immunotherapy","score":0.7929999828338623},{"id":"https://openalex.org/keywords/wt1","display_name":"WT1","score":0.7440000176429749},{"id":"https://openalex.org/keywords/prame","display_name":"PRAME","score":0.9990000128746033},{"id":"https://openalex.org/keywords/ovarian-cancer","display_name":"ovarian cancer","score":0.6700000166893005},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.9990000128746033},{"id":"https://openalex.org/keywords/tgf-beta-receptor-ii","display_name":"TGFBR2","score":0.6549999713897705},{"id":"https://openalex.org/keywords/t-cell-persistence","display_name":"T cell persistence","score":0.6169999837875366},{"id":"https://openalex.org/keywords/t-cell-expansion","display_name":"T cell expansion","score":0.37400001287460327},{"id":"https://openalex.org/keywords/th1-cytokines","display_name":"Th1 cytokines","score":0.6449999809265137},{"id":"https://openalex.org/keywords/crispr-cas9-genome-editing","display_name":"CRISPR/Cas9 genome editing","score":0.6880000233650208},{"id":"https://openalex.org/keywords/tumor-rechallenge","display_name":"tumor rechallenge","score":0.46000000834465027},{"id":"https://openalex.org/keywords/hla-class-i-restriction","display_name":"HLA class I restriction","score":0.49300000071525574}],"concepts":[{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.579735517501831},{"id":"https://openalex.org/C2778468042","wikidata":"https://www.wikidata.org/wiki/Q273976","display_name":"Blockade","level":3,"score":0.5626435279846191},{"id":"https://openalex.org/C24998067","wikidata":"https://www.wikidata.org/wiki/Q4114622","display_name":"Stimulation","level":2,"score":0.5331994891166687},{"id":"https://openalex.org/C104304963","wikidata":"https://www.wikidata.org/wiki/Q5316114","display_name":"Durability","level":2,"score":0.47674238681793213},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4727930724620819},{"id":"https://openalex.org/C19317047","wikidata":"https://www.wikidata.org/wiki/Q412037","display_name":"T-cell receptor","level":4,"score":0.438981294631958},{"id":"https://openalex.org/C167672396","wikidata":"https://www.wikidata.org/wiki/Q417800","display_name":"CD8","level":3,"score":0.4201992154121399},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.3190150856971741},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2131456434726715},{"id":"https://openalex.org/C192562407","wikidata":"https://www.wikidata.org/wiki/Q228736","display_name":"Materials science","level":0,"score":0.2022278606891632},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.19391527771949768},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.176423579454422},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.14812108874320984},{"id":"https://openalex.org/C159985019","wikidata":"https://www.wikidata.org/wiki/Q181790","display_name":"Composite material","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1136/jitc-2024-sitc2024.0388","doi":"https://doi.org/10.1136/jitc-2024-sitc2024.0388","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2024-sitc2024.0388","pdf_url":null,"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":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","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-2024-sitc2024.0388","doi":"https://doi.org/10.1136/jitc-2024-sitc2024.0388","is_oa":true,"landing_page_url":"https://doi.org/10.1136/jitc-2024-sitc2024.0388","pdf_url":null,"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":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","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":0.9763000011444092}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7171486058","https://openalex.org/W4399170928","https://openalex.org/W7118082758","https://openalex.org/W3212213571","https://openalex.org/W4409634430","https://openalex.org/W4392955797","https://openalex.org/W4404064934","https://openalex.org/W4320896665","https://openalex.org/W4210859154","https://openalex.org/W4212946091"],"abstract_inverted_index":{"Background":[0],"Adoptive":[1],"cell":[2,8,85,140,163,177,265,270,380],"therapy":[3],"using":[4,168],"tumor":[5,62,134,146,173,300,311,315],"antigen-targeting":[6],"T":[7,84,113,162,205,264],"receptors":[9,256,291,369],"(TCRs)":[10],"offers":[11],"a":[12,353,371],"compelling":[13],"approach":[14,373],"to":[15,24,31,57,65,110,210,218,248,294],"treat":[16],"both":[17],"hematological":[18],"cancers":[19],"and":[20,28,88,150,158,171,176,188,207,234,262,275,306,330,403],"solid":[21],"tumors":[22],"due":[23],"broad":[25],"antigen":[26,328],"accessibility":[27],"the":[29,94,327,342,347,376],"ability":[30],"target":[32],"specific":[33],"cancer":[34,229],"neoantigens.":[35],"However,":[36,214],"unlike":[37],"clinically":[38],"validated":[39],"second":[40,354],"generation":[41],"CAR-T":[42],"cells":[43,54,96,114,147,252,288],"bearing":[44],"built-in":[45],"co-stimulatory":[46,125],"signaling":[47],"modules":[48],"(i.e.,":[49],"41BB":[50],"or":[51,97,137,230],"CD28),":[52],"TCR-T":[53,139,212],"receive":[55],"little":[56],"no":[58],"co-stimulation":[59],"within":[60],"most":[61],"microenvironments":[63],"leading":[64],"relatively":[66],"muted":[67],"cellular":[68],"responses.":[69,101],"Additionally,":[70],"HLA":[71],"class":[72],"I":[73],"restricted":[74],"TCRs,":[75],"even":[76],"those":[77],"with":[78,115,128,243,283,393],"high":[79,355],"affinity,":[80],"elicit":[81],"minimal":[82],"CD4+":[83,204,261],"helper":[86,206],"activity":[87,209,246,344],"thus":[89],"do":[90],"not":[91,334],"maximally":[92],"mobilize":[93],"CD8+TCR-T":[95],"host":[98],"anti-tumor":[99,221],"immune":[100],"Methods":[102],"To":[103],"address":[104],"these":[105,254],"limitations,":[106],"we":[107],"used":[108],"CRISPR/Cas9":[109,194,361],"engineer":[111],"human":[112],"site-specific":[116,196],"insertion":[117],"of":[118,198,227,236,338,365,378],"synthetic":[119],"chimeric":[120],"CD8":[121],"constructs":[122,239],"containing":[123],"intracellular":[124],"domains":[126],"along":[127],"transgenic":[129],"TCRs":[130],"targeting":[131,358],"relevant":[132],"shared":[133],"antigens":[135],"(WT1":[136],"PRAME).":[138],"potency":[141,164,377],"was":[142,165,216,317,350],"evaluated":[143,166],"in-vitro":[144],"against":[145],"in":[148,223,260,269,319,352,391],"acute":[149],"long-term":[151,272,308],"serial":[152],"rechallenge":[153],"cytotoxicity":[154],"assays,":[155,157],"proliferation":[156],"cytokine":[159,186,278],"release":[160],"assays.":[161],"in-vivo":[167,304],"challenging":[169,224],"ovarian":[170,228,299],"AML":[172,322],"xenograft":[174],"models":[175,226],"persistence":[178],"monitored":[179],"by":[180,346,396],"ddPCR.":[181],"Further":[182],"mechanistic":[183],"interrogation":[184],"included":[185],"profiling":[187],"multiparameter":[189],"flow":[190],"cytometric":[191],"phenotyping.":[192],"Results":[193],"mediated":[195],"integration":[197,364],"wild":[199],"type":[200],"CD8\u03b1\u03b2":[201],"conferred":[202],"robust":[203,303],"cytolytic":[208],"WT1-targeting":[211],"cells.":[213],"this":[215],"insufficient":[217],"drive":[219],"curative":[220],"responses":[222],"mouse":[225],"AML.":[231],"Systematic":[232],"design":[233],"screening":[235],"CD8-co-stimulatory":[237],"fusion":[238,368],"identified":[240],"CD8-41BB":[241,255,290,339,348,367],"designs":[242],"substantially":[244],"increased":[245],"relative":[247],"wild-type":[249],"CD8\u03b1\u03b2.":[250],"WT1-TCR-T":[251,287],"co-expressing":[253,289],"demonstrated":[257],"several-fold":[258],"improvement":[259],"CD8+":[263],"activity,":[266],"including":[267],"increases":[268],"proliferation,":[271],"killing":[273],"ability,":[274],"polarized":[276],"Th1-type":[277],"secretion.":[279],"Remarkably,":[280],"when":[281],"combined":[282],"TGF\u03b2R2":[284],"gene":[285],"disruption,":[286],"were":[292],"able":[293],"completely":[295],"regress":[296],"established":[297],"large":[298],"xenografts,":[301],"showed":[302],"expansion,":[305],"provided":[307],"protection":[309],"from":[310],"rechallenge.":[312],"Similarly,":[313],"complete":[314],"clearance":[316],"achieved":[318],"an":[320],"aggressive":[321],"cell-line":[323],"derived":[324],"model.":[325],"Importantly,":[326],"specificity":[329],"HLA-A*02:01":[331],"restriction,":[332],"did":[333],"change":[335],"upon":[336],"expression":[337],"receptors.":[340],"Lastly,":[341],"enhanced":[343],"driven":[345],"receptor":[349],"confirmed":[351],"avidity":[356],"TCR":[357],"PRAME.":[359],"Conclusions":[360],"based":[362],"targeted":[363],"novel":[366],"represents":[370],"next-generation":[372],"for":[374],"enhancing":[375],"TCR-based":[379],"therapies.":[381],"Ethics":[382],"Approval":[383],"Animal":[384,401],"studies":[385],"described":[386],"here":[387],"have":[388],"been":[389],"performed":[390],"compliance":[392],"protocols":[394],"approved":[395],"Intellia":[397],"Therapeutics\u2019":[398],"IACUC":[399],"(Institutional":[400],"Care":[402],"Use":[404],"Committee).":[405]},"counts_by_year":[],"updated_date":"2026-11-02T09:45:03.842371","created_date":"2024-11-06T00:00:00"}