{"id":"https://openalex.org/W7214168587","doi":"https://doi.org/10.64898/2026.09.23.753936","title":"Size-dependent effect of site-specific polyethylene glycol modification of trastuzumab on the antibody functions","display_name":"Size-dependent effect of site-specific polyethylene glycol modification of trastuzumab on the antibody functions","publication_year":2026,"publication_date":"2026-09-24","ids":{"openalex":"https://openalex.org/W7214168587","doi":"https://doi.org/10.64898/2026.09.23.753936"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.23.753936","doi":"https://doi.org/10.64898/2026.09.23.753936","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.23.753936","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/24/2026.09.23.753936.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/24/2026.09.23.753936.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5064618670","display_name":"Yuya Tsutsui","orcid":"https://orcid.org/0000-0002-9220-4857","observed_orcids":["https://orcid.org/0000-0002-9220-4857"]},"institutions":[{"id":"https://openalex.org/I22299242","display_name":"Kyoto University","ror":"https://ror.org/02kpeqv85","country_code":"JP","type":"education","lineage":["https://openalex.org/I22299242"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yuya Tsutsui","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan","institution_ids":["https://openalex.org/I22299242"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013135912","display_name":"Hiroaki Ohno","orcid":"https://orcid.org/0000-0002-3246-4809","observed_orcids":["https://orcid.org/0000-0002-3246-4809"]},"institutions":[{"id":"https://openalex.org/I22299242","display_name":"Kyoto University","ror":"https://ror.org/02kpeqv85","country_code":"JP","type":"education","lineage":["https://openalex.org/I22299242"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Hiroaki Ohno","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan","institution_ids":["https://openalex.org/I22299242"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5090009166","display_name":"Hiroki Akiba","orcid":"https://orcid.org/0000-0002-1450-5873","observed_orcids":["https://orcid.org/0000-0002-1450-5873"]},"institutions":[{"id":"https://openalex.org/I22299242","display_name":"Kyoto University","ror":"https://ror.org/02kpeqv85","country_code":"JP","type":"education","lineage":["https://openalex.org/I22299242"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Hiroki Akiba","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan"],"raw_orcid":"https://orcid.org/0000-0002-1450-5873","affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan","institution_ids":["https://openalex.org/I22299242"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5013135912","https://openalex.org/A5090009166"],"corresponding_institution_ids":["https://openalex.org/I22299242"],"apc_list":null,"apc_paid":null,"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":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9984999895095825,"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"}},"topics":[{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9984999895095825,"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/T11124","display_name":"Protein purification and stability","score":0.00039999998989515007,"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/T12477","display_name":"Toxin Mechanisms and Immunotoxins","score":9.999999747378752e-05,"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/trastuzumab","display_name":"trastuzumab","score":0.9739999771118164},{"id":"https://openalex.org/keywords/site-specific-pegylation","display_name":"site-specific PEGylation","score":0.9120000004768372},{"id":"https://openalex.org/keywords/antibody-modification","display_name":"antibody modification","score":0.6000000238418579},{"id":"https://openalex.org/keywords/antibody-dependent-cellular-cytotoxicity","display_name":"antibody-dependent cellular cytotoxicity","score":0.9509999752044678},{"id":"https://openalex.org/keywords/fcgammariiia-binding","display_name":"Fc\u03b3RIIIa binding","score":0.8360000252723694},{"id":"https://openalex.org/keywords/antigen-binding","display_name":"antigen binding","score":0.871999979019165},{"id":"https://openalex.org/keywords/antibody-effector-functions","display_name":"antibody effector functions","score":0.7049999833106995},{"id":"https://openalex.org/keywords/antibody-oligonucleotide-conjugates","display_name":"antibody-oligonucleotide conjugates","score":0.7210000157356262}],"concepts":[{"id":"https://openalex.org/C2776964284","wikidata":"https://www.wikidata.org/wiki/Q410083","display_name":"Polyethylene glycol","level":2,"score":0.7994999885559082},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7688000202178955},{"id":"https://openalex.org/C40677261","wikidata":"https://www.wikidata.org/wiki/Q21418091","display_name":"Antibody-dependent cell-mediated cytotoxicity","level":4,"score":0.7480000257492065},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.73580002784729},{"id":"https://openalex.org/C197336794","wikidata":"https://www.wikidata.org/wiki/Q5161150","display_name":"Conjugate","level":2,"score":0.6492000222206116},{"id":"https://openalex.org/C54400483","wikidata":"https://www.wikidata.org/wiki/Q1793202","display_name":"PEG ratio","level":2,"score":0.6244999766349792},{"id":"https://openalex.org/C2779149719","wikidata":"https://www.wikidata.org/wiki/Q682252","display_name":"PEGylation","level":3,"score":0.5672000050544739},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.5565000176429749},{"id":"https://openalex.org/C2779786085","wikidata":"https://www.wikidata.org/wiki/Q412616","display_name":"Trastuzumab","level":4,"score":0.5378000140190125},{"id":"https://openalex.org/C51785407","wikidata":"https://www.wikidata.org/wiki/Q2627568","display_name":"Effector","level":2,"score":0.49070000648498535},{"id":"https://openalex.org/C184133267","wikidata":"https://www.wikidata.org/wiki/Q5090480","display_name":"Chemical modification","level":2,"score":0.4846000075340271},{"id":"https://openalex.org/C115537861","wikidata":"https://www.wikidata.org/wiki/Q7645993","display_name":"Surface modification","level":2,"score":0.48420000076293945},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.3910999894142151},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.36079999804496765},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.34950000047683716},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.34940001368522644},{"id":"https://openalex.org/C147483822","wikidata":"https://www.wikidata.org/wiki/Q103537","display_name":"Antigen","level":2,"score":0.3472999930381775},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.3319999873638153},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.3310999870300293},{"id":"https://openalex.org/C521977710","wikidata":"https://www.wikidata.org/wiki/Q81163","display_name":"Polymer","level":2,"score":0.32829999923706055},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.3140000104904175},{"id":"https://openalex.org/C112613896","wikidata":"https://www.wikidata.org/wiki/Q898370","display_name":"Conjugated system","level":3,"score":0.2985000014305115},{"id":"https://openalex.org/C161733203","wikidata":"https://www.wikidata.org/wiki/Q911828","display_name":"Reporter gene","level":4,"score":0.2973000109195709},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.28290000557899475},{"id":"https://openalex.org/C2776120743","wikidata":"https://www.wikidata.org/wiki/Q3271540","display_name":"Mechanism of action","level":3,"score":0.2624000012874603},{"id":"https://openalex.org/C116073593","wikidata":"https://www.wikidata.org/wiki/Q864491","display_name":"Biological activity","level":3,"score":0.2542000114917755},{"id":"https://openalex.org/C54009773","wikidata":"https://www.wikidata.org/wiki/Q1429031","display_name":"Transfection","level":3,"score":0.25029999017715454}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.23.753936","doi":"https://doi.org/10.64898/2026.09.23.753936","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.23.753936","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/24/2026.09.23.753936.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.23.753936","doi":"https://doi.org/10.64898/2026.09.23.753936","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.23.753936","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/24/2026.09.23.753936.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.6240000128746033,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7214168587.pdf","grobid_xml":"https://content.openalex.org/works/W7214168587.grobid-xml"},"referenced_works_count":32,"referenced_works":["https://openalex.org/W1578375703","https://openalex.org/W1979230226","https://openalex.org/W2006008435","https://openalex.org/W2034502454","https://openalex.org/W2041770021","https://openalex.org/W2077812250","https://openalex.org/W2116150122","https://openalex.org/W2118964148","https://openalex.org/W2571138221","https://openalex.org/W2592514789","https://openalex.org/W2766298702","https://openalex.org/W2943244258","https://openalex.org/W2964281619","https://openalex.org/W3138693416","https://openalex.org/W3186457805","https://openalex.org/W3207751091","https://openalex.org/W4210757284","https://openalex.org/W4284671925","https://openalex.org/W4376618825","https://openalex.org/W4388282536","https://openalex.org/W4390848939","https://openalex.org/W4401273592","https://openalex.org/W4401935619","https://openalex.org/W4406614291","https://openalex.org/W4409148758","https://openalex.org/W4412197680","https://openalex.org/W4414084536","https://openalex.org/W4414757289","https://openalex.org/W4416094626","https://openalex.org/W7140164257","https://openalex.org/W7162320128","https://openalex.org/W7163890748"],"related_works":["https://openalex.org/W2045767384","https://openalex.org/W4379983571","https://openalex.org/W3087740603","https://openalex.org/W7051861500","https://openalex.org/W2322951142","https://openalex.org/W2041760089","https://openalex.org/W1511424309","https://openalex.org/W2382732453","https://openalex.org/W4417048935","https://openalex.org/W2054708031"],"abstract_inverted_index":{"Abstract":[0],"Polymer":[1],"modification":[2,31,68,119,153],"of":[3,38,66,73,117,133,154],"antibodies":[4],"has":[5,23],"attracted":[6],"attention":[7],"for":[8,124,150],"enhancing":[9],"antibody":[10,42,77,136],"functionality.":[11],"Modification":[12],"with":[13,103],"polyethylene":[14],"glycol":[15],"(PEG)":[16],"or":[17],"biopolymers":[18],"such":[19,44],"as":[20,45],"antibody-oligonucleotide":[21],"conjugates":[22],"been":[24,34],"investigated.":[25],"Although":[26],"direct":[27],"effects":[28,37,65],"at":[29],"the":[30,64,67,71,99,104,115,118,130,134,151],"site":[32,69,120],"have":[33],"understood,":[35],"distal":[36],"modifications":[39],"on":[40,76],"intrinsic":[41],"functions":[43],"antigen-binding":[46],"and":[47,70,95,106],"Fc":[48],"receptor-binding":[49],"activities":[50],"remain":[51],"poorly":[52],"characterized.":[53],"In":[54],"this":[55],"study,":[56],"we":[57],"prepared":[58],"site-specifically":[59],"PEGylated":[60],"trastuzumab":[61],"to":[62],"evaluate":[63],"size":[72],"PEG":[74],"chains":[75],"functions.":[78],"Reporter":[79],"gene":[80],"assays":[81],"revealed":[82],"a":[83,93,111,138],"significant":[84],"reduction":[85,100],"in":[86,92,101,110,141],"antibody-dependent":[87],"cell":[88],"cytotoxicity":[89],"(ADCC)":[90],"activity":[91],"site-":[94],"size-dependent":[96,112],"manner.":[97,113],"Both":[98],"interaction":[102],"antigen":[105],"Fc\u03b3RIIIa":[107],"were":[108],"observed":[109,123],"Interestingly,":[114],"effect":[116],"was":[121],"only":[122],"ADCC":[125],"activity,":[126],"which":[127],"suggests":[128],"that":[129],"higher-order":[131],"structure":[132],"modified":[135],"plays":[137],"critical":[139],"role":[140],"effector":[142],"function.":[143],"These":[144],"results":[145],"provide":[146],"molecular":[147],"design":[148],"guidelines":[149],"polymer":[152],"antibodies.":[155]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-09-25T00:00:00"}