{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:17:17Z","timestamp":1789690637718,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>Engineering antibodies to elicit antibody\u2010dependent cell\u2010mediated cytotoxicity (ADCC) can be used to eliminate target cells. Here, we described how single domain VHH arms on a bispecific antibody (BsAb) format can be engineered to modulate cell binding and ADCC activity. The BsAbs, comprising two anti\u2010epidermal growth factor receptor (EGFR) nanobodies, 7D12 and EGA1, were engineered onto a human IgG1 Fc domain in monovalent, bivalent, and tandem formats. While 7D12 had a stronger ADCC activity than EGA1, the tandem 7D12\u2010EGA1 mediated a significantly stronger ADCC activity without significant changes in cell binding in numerous cancer cell lines. In addition, we present how the molecular design of the tandem 7D12 and EGA1 nanobodies could cross\u2010link two different EGFR molecules to obtain stronger ADCC activity.<\/jats:p>","DOI":"10.1002\/2211-5463.70166","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T08:36:05Z","timestamp":1763627765000},"page":"1030-1043","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Engineering tandem\n                    <scp>VHHs<\/scp>\n                    to target different epitopes to enhance antibody\u2010dependent cell\u2010mediated cytotoxicity"],"prefix":"10.1002","volume":"16","author":[{"given":"Yuqiang","family":"Xu","sequence":"first","affiliation":[{"name":"Research &amp; Development Department Tavotek Biotherapeutics  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department Tavotek Biotherapeutics  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Chen","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department Tavotek Biotherapeutics  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department Tavotek Biotherapeutics  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jin","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department Tavotek Biotherapeutics  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-404X","authenticated-orcid":false,"given":"Mark L.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department Tavotek Biotherapeutics  Suzhou China"},{"name":"Research &amp; Development Tavotek Biotherapeutics  Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.12.38"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900985"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2018.1466767"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.913215"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4835"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-687749"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003032"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdr484"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2010.01.011"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023023370"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2022.08.006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00501-8"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0696"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12343"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00740"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.6.11.1161"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2016.1212665"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026620666200303123102"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008209720526"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10372"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010395940"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2006.42.11.1032061"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3388"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.24.6116"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-0849"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13071042"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00666-5"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26145"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2013.05.008"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2010.03.020"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.9b01280"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202103463"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220145110"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.169"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12010003"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000303"},{"key":"e_1_2_10_39_1","first-page":"24","article-title":"Structural insights into the binding of red fluorescent protein mCherry\u2010specific nanobodies","author":"Liang H","year":"2023","journal-title":"Int J Mol Sci"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-62606-7"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2013.06.036"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.2.2.11158"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb300455f"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.3c00481"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat5775"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01805-9"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157788"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.03.021"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.296"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.028753"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00520"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-380121"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37029-3"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.70166","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/2211-5463.70166","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.70166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:19:54Z","timestamp":1778941194000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.70166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/2211-5463.70166"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.70166","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v4\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.70166\/v4\/response1","asserted-by":"object"}]},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]},"assertion":[{"value":"2025-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}