{"id":"https://openalex.org/W3211937637","doi":null,"title":"Establishing a scalable manufacturing process for the clinical scale production of CAR-T cell therapies in stirred-tank bioreactors","display_name":"Establishing a scalable manufacturing process for the clinical scale production of CAR-T cell therapies in stirred-tank bioreactors","publication_year":2021,"publication_date":"2021-05-28","ids":{"openalex":"https://openalex.org/W3211937637","mag":"3211937637"},"language":"en","primary_location":{"id":"pmh:oai:eprints.ucl.ac.uk.OAI2:10128716","doi":null,"is_oa":false,"landing_page_url":"https://discovery.ucl.ac.uk/id/eprint/10128716/","pdf_url":null,"source":{"id":"https://openalex.org/S4306400024","display_name":"UCL Discovery (University College London)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I45129253","host_organization_name":"University College London","host_organization_lineage":["https://openalex.org/I45129253"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Doctoral thesis, UCL (University College London).","raw_type":"Thesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5013146703","display_name":"Elena Costariol","orcid":"https://orcid.org/0000-0002-3801-5684","observed_orcids":["https://orcid.org/0000-0002-3801-5684"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Elena Costariol","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-3801-5684","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5013146703"],"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":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11491","display_name":"CAR-T cell therapy research","score":0.9872999787330627,"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":0.9872999787330627,"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/T10864","display_name":"Fluid Dynamics and Mixing","score":0.003800000064074993,"subfield":{"id":"https://openalex.org/subfields/1507","display_name":"Fluid Flow and Transfer Processes"},"field":{"id":"https://openalex.org/fields/15","display_name":"Chemical Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11663","display_name":"Viral Infectious Diseases and Gene Expression in Insects","score":0.0010000000474974513,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/car-t-cell-therapy","display_name":"CAR T-cell therapy","score":0.953000009059906},{"id":"https://openalex.org/keywords/stirred-tank-bioreactor","display_name":"stirred tank bioreactor","score":0.9279999732971191},{"id":"https://openalex.org/keywords/stirring-speed","display_name":"stirring speed","score":0.8309999704360962},{"id":"https://openalex.org/keywords/shear-stress","display_name":"shear stress","score":0.5690000057220459},{"id":"https://openalex.org/keywords/allogeneic-car-t-cells","display_name":"allogeneic CAR T cells","score":0.6919999718666077},{"id":"https://openalex.org/keywords/autologous-car-t","display_name":"autologous CAR-T","score":0.9869999885559082},{"id":"https://openalex.org/keywords/cell-proliferation","display_name":"cell proliferation","score":0.4620000123977661},{"id":"https://openalex.org/keywords/dynabeads","display_name":"Dynabeads","score":0.7630000114440918},{"id":"https://openalex.org/keywords/scalable-bioprocessing","display_name":"scalable bioprocessing","score":0.531000018119812}],"concepts":[{"id":"https://openalex.org/C168170006","wikidata":"https://www.wikidata.org/wiki/Q864699","display_name":"Bioreactor","level":2,"score":0.8778249025344849},{"id":"https://openalex.org/C2777874358","wikidata":"https://www.wikidata.org/wiki/Q7389060","display_name":"SCALE-UP","level":2,"score":0.5709933042526245},{"id":"https://openalex.org/C139149728","wikidata":"https://www.wikidata.org/wiki/Q335201","display_name":"Laboratory flask","level":2,"score":0.5255400538444519},{"id":"https://openalex.org/C67334161","wikidata":"https://www.wikidata.org/wiki/Q457904","display_name":"Continuous stirred-tank reactor","level":2,"score":0.5136227011680603},{"id":"https://openalex.org/C2780513914","wikidata":"https://www.wikidata.org/wiki/Q18210350","display_name":"Bottleneck","level":2,"score":0.4908323884010315},{"id":"https://openalex.org/C21880701","wikidata":"https://www.wikidata.org/wiki/Q2144042","display_name":"Process engineering","level":1,"score":0.4667888581752777},{"id":"https://openalex.org/C98045186","wikidata":"https://www.wikidata.org/wiki/Q205663","display_name":"Process (computing)","level":2,"score":0.44011369347572327},{"id":"https://openalex.org/C136229726","wikidata":"https://www.wikidata.org/wiki/Q327092","display_name":"Biomedical engineering","level":1,"score":0.34963923692703247},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.34732696413993835},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.30853503942489624},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.28259432315826416},{"id":"https://openalex.org/C42360764","wikidata":"https://www.wikidata.org/wiki/Q83588","display_name":"Chemical engineering","level":1,"score":0.12645918130874634},{"id":"https://openalex.org/C21547014","wikidata":"https://www.wikidata.org/wiki/Q1423657","display_name":"Operations management","level":1,"score":0.11690706014633179},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.10375121235847473},{"id":"https://openalex.org/C111919701","wikidata":"https://www.wikidata.org/wiki/Q9135","display_name":"Operating system","level":1,"score":0.07521206140518188},{"id":"https://openalex.org/C147789679","wikidata":"https://www.wikidata.org/wiki/Q11372","display_name":"Physical chemistry","level":1,"score":0.0},{"id":"https://openalex.org/C74650414","wikidata":"https://www.wikidata.org/wiki/Q11397","display_name":"Classical mechanics","level":1,"score":0.0},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:eprints.ucl.ac.uk.OAI2:10128716","doi":null,"is_oa":false,"landing_page_url":"https://discovery.ucl.ac.uk/id/eprint/10128716/","pdf_url":null,"source":{"id":"https://openalex.org/S4306400024","display_name":"UCL Discovery (University College London)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I45129253","host_organization_name":"University College London","host_organization_lineage":["https://openalex.org/I45129253"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Doctoral thesis, UCL (University College London).","raw_type":"Thesis"},{"id":"mag:3211937637","doi":null,"is_oa":false,"landing_page_url":"https://discovery.ucl.ac.uk/id/eprint/10128716/","pdf_url":null,"source":{"id":"https://openalex.org/S4306508231","display_name":"Doctoral thesis, UCL (University College London).","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":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"Doctoral thesis, UCL (University College London).","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9074000120162964,"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/W2951554930","https://openalex.org/W3037107396","https://openalex.org/W2946315272","https://openalex.org/W3026296649","https://openalex.org/W2945921298","https://openalex.org/W4407573048","https://openalex.org/W4398193786","https://openalex.org/W4400233541","https://openalex.org/W2065946908","https://openalex.org/W2945846133"],"abstract_inverted_index":{"CAR-T":[0,27,34,119,160,192],"immunotherapies":[1,19],"present":[2],"a":[3,40,67,76,88,275,325],"novel":[4],"therapeutic":[5],"modality":[6],"for":[7,57,141],"the":[8,15,21,48,154,186,191,232,240,243,249,253,284,287,294,302,330],"treatment":[9],"of":[10,17,23,26,79,156,176,203,242],"various":[11],"blood":[12],"tumours.":[13],"However,":[14],"development":[16],"such":[18,104],"requires":[20],"manufacture":[22],"large":[24],"numbers":[25],"cells":[28,35,120,161,193,207,254],"(2-6":[29],"x":[30],"108":[31],"total":[32],"viable":[33,200],"per":[36],"dose),":[37],"which":[38,137],"remains":[39],"major":[41],"translational":[42],"and":[43,51,97,118,134,144,158,179,219,227,235,245],"commercial":[44],"bottleneck":[45],"due":[46,282],"to":[47,64,82,112,182,196,248,269,274,283,291,297,320],"manual,":[49],"small-scale,":[50],"often":[52],"static":[53,171,223,257,315],"culture":[54,229],"systems":[55,61,218],"used":[56,140,296],"their":[58],"production.":[59],"Such":[60],"are":[62,72,94,318],"easy":[63],"use":[65],"in":[66,101,124,149,165,169,185],"pre-clinical":[68],"research":[69],"settings,":[70],"but":[71],"not":[73,99],"efficient":[74],"when":[75],"higher":[77,265,270],"number":[78],"doses":[80],"need":[81],"be":[83,122,139],"produced.":[84],"Furthermore,":[85,147],"there":[86,305],"is":[87,213,280,306],"general":[89],"concern":[90],"that":[91,114,153,264,309],"primary":[92,115],"T-cells":[93,117,157,310],"shear":[95],"sensitive":[96,319],"do":[98],"grow":[100],"agitated":[102],"systems,":[103],"as":[105,259],"stirred-tank":[106,125,166,189,326],"bioreactors.":[107],"This":[108,212,278],"doctoral":[109],"thesis":[110,151],"aims":[111],"demonstrate":[113],"human":[116],"can":[121,138],"cultivated":[123],"bioreactors":[126,167],"at":[127,239,286,329],"different":[128],"scales":[129],"(15":[130],"ml,":[131,133],"250":[132,188],"1":[135],"L),":[136],"both":[142],"autologous":[143],"allogeneic":[145],"products.":[146],"data":[148,303],"this":[150],"shows":[152],"growth":[155],"transduced":[159],"was":[162,237,246,262],"significantly":[163,220],"better":[164,221,276],"than":[168,222],"T-flask":[170],"culture.":[172],"At":[173],"agitation":[174,266,289,331],"speeds":[175,332],"200":[177],"rpm":[178],"greater":[180],"(up":[181],"500":[183],"rpm)":[184],"ambr":[187],"bioreactor,":[190],"were":[194],"able":[195],"proliferate":[197],"effectively,":[198],"reaching":[199],"cell":[201,233],"densities":[202],">":[204],"5":[205],"x106":[206],"ml-1":[208],"over":[209],"7":[210],"days.":[211],"comparable":[214],"with":[215],"current":[216],"expansion":[217,224,244],"platforms":[225],"(T-flasks":[226],"gas-permeable":[228],"bags).":[230],"Importantly,":[231,300],"quality":[234],"potency":[236],"assessed":[238],"end":[241],"equivalent":[247],"one":[250],"presented":[251],"by":[252],"grown":[255,313],"under":[256,314],"conditions":[258,316],"control.":[260],"It":[261],"demonstrated":[263],"rates,":[267],"corresponding":[268],"power":[271],"inputs":[272],"lead":[273],"proliferation.":[277],"improvement":[279],"likely":[281],"inability":[285],"lower":[288],"rates":[290],"effectively":[292],"suspend":[293],"Dynabeads":[295],"activate":[298],"T-cells.":[299],"from":[301],"obtained,":[304],"no":[307],"indication":[308],"prefer":[311],"being":[312],"or":[317],"fluid":[321],"dynamic":[322],"stresses":[323],"within":[324],"bioreactor":[327],"system":[328],"investigated.":[333]},"counts_by_year":[],"updated_date":"2026-09-09T07:26:56.047234","created_date":"2021-11-22T00:00:00"}