{"id":"https://openalex.org/W2169799220","doi":"https://doi.org/10.1002/bit.1020","title":"Rapamycin reduces hybridoma cell death and enhances monoclonal antibody production","display_name":"Rapamycin reduces hybridoma cell death and enhances monoclonal antibody production","publication_year":2001,"publication_date":"2001-01-01","ids":{"openalex":"https://openalex.org/W2169799220","doi":"https://doi.org/10.1002/bit.1020","mag":"2169799220","pmid":"https://pubmed.ncbi.nlm.nih.gov/11400101"},"language":"en","primary_location":{"id":"doi:10.1002/bit.1020","doi":"https://doi.org/10.1002/bit.1020","is_oa":false,"landing_page_url":"https://doi.org/10.1002/bit.1020","pdf_url":null,"source":{"id":"https://openalex.org/S151564723","display_name":"Biotechnology and Bioengineering","issn_l":"0006-3592","issn":["0006-3592","1097-0290"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biotechnology and Bioengineering","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"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/A5045809500","display_name":"R. Robert Balcarcel","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"R. Robert Balcarcel","raw_affiliation_strings":["Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, Massachusetts 02139, USA","fax: 617-253-3122","telephone: 617-253-4583"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, Massachusetts 02139, USA","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"fax: 617-253-3122","institution_ids":[]},{"raw_affiliation_string":"telephone: 617-253-4583","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5009763658","display_name":"Gregory N Stephanopoulos","orcid":"https://orcid.org/0000-0001-6909-4568","observed_orcids":["https://orcid.org/0000-0001-6909-4568"]},"institutions":[{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Gregory Stephanopoulos","raw_affiliation_strings":["Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, Massachusetts, 02139, USA; telephone: 617-253-4583; fax: 617-253-3122","Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, Massachusetts, 02139, USA","fax: 617-253-3122","telephone: 617-253-4583"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, Massachusetts, 02139, USA; telephone: 617-253-4583; fax: 617-253-3122","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, Massachusetts, 02139, USA","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"fax: 617-253-3122","institution_ids":[]},{"raw_affiliation_string":"telephone: 617-253-4583","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5009763658"],"corresponding_institution_ids":["https://openalex.org/I63966007"],"apc_list":{"value":5060,"currency":"USD","value_usd":5060},"apc_paid":null,"fwci":1.0473,"has_fulltext":false,"cited_by_count":58,"citation_normalized_percentile":{"value":0.7503158,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":97},"biblio":{"volume":"76","issue":"1","first_page":"1","last_page":"10"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11663","display_name":"Viral Infectious Diseases and Gene Expression in Insects","score":0.5214999914169312,"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/T11663","display_name":"Viral Infectious Diseases and Gene Expression in Insects","score":0.5214999914169312,"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/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.3801000118255615,"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"}},{"id":"https://openalex.org/T10864","display_name":"Fluid Dynamics and Mixing","score":0.01979999989271164,"subfield":{"id":"https://openalex.org/subfields/2204","display_name":"Biomedical Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/rapamycin","display_name":"rapamycin","score":1.0},{"id":"https://openalex.org/keywords/monoclonal-antibody-production","display_name":"monoclonal antibody production","score":0.984000027179718},{"id":"https://openalex.org/keywords/g1-cell-cycle-arrest","display_name":"G1 cell cycle arrest","score":0.7749999761581421},{"id":"https://openalex.org/keywords/fed-batch-fermentation","display_name":"fed-batch fermentation","score":0.9070000052452087},{"id":"https://openalex.org/keywords/viable-cell-density","display_name":"viable cell density","score":0.7730000019073486},{"id":"https://openalex.org/keywords/signal-transduction","display_name":"signal transduction","score":0.7490000128746033}],"concepts":[{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.7252014875411987},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.6595616936683655},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6369915008544922},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.6232062578201294},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.5316503643989563},{"id":"https://openalex.org/C53227056","wikidata":"https://www.wikidata.org/wiki/Q189152","display_name":"Viability assay","level":3,"score":0.4827786982059479},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.46312814950942993},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.44519948959350586},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.4258878231048584},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.41930100321769714},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.29084140062332153},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.2364344596862793},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.1794576644897461},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.17859309911727905},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.16161876916885376},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000911","descriptor_name":"Antibodies, Monoclonal","qualifier_ui":"Q000096","qualifier_name":"biosynthesis","is_major_topic":true},{"descriptor_ui":"D000917","descriptor_name":"Antibody Formation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D001709","descriptor_name":"Biotechnology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002453","descriptor_name":"Cell Cycle","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D002453","descriptor_name":"Cell Cycle","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D002455","descriptor_name":"Cell Division","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002470","descriptor_name":"Cell Survival","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D006825","descriptor_name":"Hybridomas","qualifier_ui":"Q000166","qualifier_name":"cytology","is_major_topic":true},{"descriptor_ui":"D006825","descriptor_name":"Hybridomas","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D006825","descriptor_name":"Hybridomas","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":true},{"descriptor_ui":"D007074","descriptor_name":"Immunoglobulin G","qualifier_ui":"Q000096","qualifier_name":"biosynthesis","is_major_topic":false},{"descriptor_ui":"D016923","descriptor_name":"Cell Death","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D020123","descriptor_name":"Sirolimus","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1002/bit.1020","doi":"https://doi.org/10.1002/bit.1020","is_oa":false,"landing_page_url":"https://doi.org/10.1002/bit.1020","pdf_url":null,"source":{"id":"https://openalex.org/S151564723","display_name":"Biotechnology and Bioengineering","issn_l":"0006-3592","issn":["0006-3592","1097-0290"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biotechnology and Bioengineering","raw_type":"journal-article"},{"id":"pmid:11400101","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/11400101","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":"Biotechnology and bioengineering","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.4000000059604645}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":42,"referenced_works":["https://openalex.org/W659226229","https://openalex.org/W1597228305","https://openalex.org/W1599727238","https://openalex.org/W1677916325","https://openalex.org/W1939283405","https://openalex.org/W1963723155","https://openalex.org/W1964219106","https://openalex.org/W1968710841","https://openalex.org/W1980298546","https://openalex.org/W1994149094","https://openalex.org/W1994968612","https://openalex.org/W2002647504","https://openalex.org/W2007298706","https://openalex.org/W2008130390","https://openalex.org/W2013276474","https://openalex.org/W2014616379","https://openalex.org/W2015277956","https://openalex.org/W2027795688","https://openalex.org/W2029059439","https://openalex.org/W2037722434","https://openalex.org/W2039460434","https://openalex.org/W2041183456","https://openalex.org/W2044416804","https://openalex.org/W2047122535","https://openalex.org/W2047247434","https://openalex.org/W2049376072","https://openalex.org/W2049883153","https://openalex.org/W2056162678","https://openalex.org/W2066321210","https://openalex.org/W2071307134","https://openalex.org/W2076799900","https://openalex.org/W2084312950","https://openalex.org/W2085841899","https://openalex.org/W2090363519","https://openalex.org/W2125099565","https://openalex.org/W2126415488","https://openalex.org/W2150399119","https://openalex.org/W2151142303","https://openalex.org/W2155059230","https://openalex.org/W2227798478","https://openalex.org/W2289990245","https://openalex.org/W2330519499"],"related_works":["https://openalex.org/W2225458843","https://openalex.org/W1979384598","https://openalex.org/W1973186984","https://openalex.org/W2354386274","https://openalex.org/W984742713","https://openalex.org/W2082762559","https://openalex.org/W2593468946","https://openalex.org/W2067912936","https://openalex.org/W7019164895","https://openalex.org/W2386229630"],"abstract_inverted_index":{"Rapamycin":[0],"was":[1,77,116],"used":[2],"as":[3],"a":[4,24,229],"medium":[5],"additive":[6],"to":[7,47,121,126,128,168,183,219,227,253],"slow":[8],"the":[9,16,20,37,41,95,101,106,110,143,190,196,246],"progression":[10,87],"of":[11,40,57,97,103,109,145,154,192,199,233,245],"CRL":[12,34,89],"1606":[13,90],"hybridomas":[14,35],"through":[15],"cell":[17,28,42,85,111,159,172,203,237,259],"cycle,":[18],"under":[19],"hypothesis":[21],"that":[22,153,248],"such":[23],"modulation":[25],"might":[26],"reduce":[27],"death.":[29],"Cell":[30],"cycle":[31,43,86,112,238],"distributions":[32],"for":[33,81,130,161],"in":[36,83,88,94,105,123,209,212],"G1":[38,107],"phase":[39,108],"ranged":[44],"from":[45,119,217],"20%":[46],"35%":[48],"during":[49,113,185],"batch,":[50],"fed-batch,":[51],"and":[52,73,79,205,261],"continuous":[53],"culture":[54,58,139,262],"experiments,":[55],"independent":[56],"time,":[59],"dilution":[60],"rate,":[61],"growth":[62,140],"rates,":[63],"or":[64],"death":[65,160],"rates.":[66],"Rapamycin,":[67],"an":[68,210],"mTOR":[69,254],"signaling":[70],"inhibitor,":[71],"immunosuppressant,":[72],"G1-phase":[74],"arresting":[75],"agent,":[76],"identified":[78],"tested":[80],"efficacy":[82],"restraining":[84],"hybridoma":[91],"cultures.":[92],"However,":[93],"presence":[96],"100":[98],"nM":[99],"rapamycin,":[100],"percentage":[102],"cells":[104],"fed-batch":[114,194],"cultures":[115,125,156],"only":[117,136],"increased":[118],"28%":[120],"31%":[122],"control":[124,155],"37%":[127],"48%":[129],"those":[131],"with":[132],"rapamycin.":[133],"Accordingly,":[134],"rapamycin":[135,146,175,200,224],"slightly":[137],"reduced":[138],"rate.":[141],"Instead,":[142],"use":[144],"more":[147,243],"notably":[148],"kept":[149],"viability":[150],"higher":[151,169],"than":[152,236],"by":[157,181],"delaying":[158],"48":[162],"h,":[163],"thereby":[164],"enabling":[165],"viable":[166,171,202],"proliferation":[167],"maximum":[170],"densities.":[173],"Furthermore,":[174],"enhanced":[176],"specific":[177,206],"monoclonal":[178,214],"antibody":[179,215],"production":[180],"up":[182],"100%":[184],"high-viability":[186],"growth.":[187],"Thus,":[188],"over":[189],"course":[191],"6-day":[193],"cultivations,":[195],"beneficial":[197],"effects":[198],"on":[201,257],"density":[204],"productivity":[207],"resulted":[208],"increase":[211],"final":[213],"titer":[216],"0.25":[218],"0.56":[220],"g/L":[221],"(124%).":[222],"As":[223],"is":[225],"reported":[226],"influence":[228,247],"much":[230],"broader":[231],"range":[232],"cellular":[234],"functions":[235],"alone,":[239],"these":[240],"findings":[241],"are":[242],"illustrative":[244],"signal":[249],"transduction":[250],"pathways":[251],"related":[252],"can":[255],"have":[256],"overall":[258],"physiology":[260],"productivity.":[263]},"counts_by_year":[{"year":2025,"cited_by_count":2},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":2},{"year":2020,"cited_by_count":3},{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":1},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":2},{"year":2013,"cited_by_count":2},{"year":2012,"cited_by_count":2}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}