{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:59:21Z","timestamp":1792173561559,"version":"4.4.0"},"reference-count":108,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Since the approval of the CD20\u2010targeting monoclonal antibody (mAb) rituximab for the treatment of lymphoma in 1997, mAb therapy has significantly transformed cancer treatment. With over 90 FDA\u2010approved mAbs for the treatment of various hematological and solid cancers, modern cancer treatment relies heavily on these therapies. The overwhelming success of mAbs as cancer therapeutics is attributed to their broad applicability, high safety profile, and precise targeting of cancer\u2010associated surface antigens. Furthermore, mAbs can induce various anti\u2010tumor cytotoxic effector mechanisms including antibody\u2010dependent cellular cytotoxicity (ADCC), antibody\u2010dependent cellular phagocytosis (ADCP), and complement\u2010dependent cytotoxicity (CDC), all of which are mediated via their fragment crystallizable (Fc) domain. Over the past decades, these effector mechanisms have been substantially improved through Fc domain engineering. In this review, we will outline the different approaches to enhance Fc effector functions via Fc engineering of mAbs, with a specific emphasis on the so\u2010called \u201cHexaBody\u201d technology, which is designed to enhance the hexamerization of mAbs on the target cell surface, thereby inducing greater complement activation, CDC, and receptor clustering. The review will summarize the development, preclinical, and clinical testing of several HexaBodies designed for the treatment of B\u2010cell malignancies, as well as the potential use of the HexaBody technology beyond Fc\u2010mediated effector functions.<\/jats:p>","DOI":"10.1111\/imr.13394","type":"journal-article","created":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T06:54:10Z","timestamp":1726296850000},"page":"456-465","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Enhancing\n                    <scp>Fc<\/scp>\n                    \u2010mediated effector functions of monoclonal antibodies: The example of\n                    <scp>HexaBodies<\/scp>"],"prefix":"10.1111","volume":"328","author":[{"given":"Hilma J.","family":"van der Horst","sequence":"first","affiliation":[{"name":"Department of Hematology Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-7187","authenticated-orcid":false,"given":"Tuna","family":"Mutis","sequence":"additional","affiliation":[{"name":"Department of Hematology Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib8040055"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.04.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(78)90333-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.70.10.2988"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0112"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/256495a0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1990.50"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.21.6851"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.6.2188"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib8030044"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0698-535"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/9872"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.149.12.3903"},{"key":"e_1_2_7_15_1","first-page":"179","volume-title":"Recombinant Antibodies for Cancer Therapy: Methods and Protocols","author":"Chowdhury PS","year":"2003"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2021.1980942"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.07.012"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-021-00471-0"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0622"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01155"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-00896-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000000983"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12103041"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00410-0"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib8020030"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2016.03.002"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-380121"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12334"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168947"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.07.009"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.97"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/35018508"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12365"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009483200"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508123103"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.28282"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0696"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(79)90010-5"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.4.2571"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.2.2.11158"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.8.4178"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(01)00010-4"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4988"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.2.1129"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)01250-0"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja306068g"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.03.021"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1998.tb01188.x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107478200"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2590347"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202069200"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210665200"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2008.11.006"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301249"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-225979"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1159\/000381524"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00646"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100399"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.02.003"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2010.12.007"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2017.1281505"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.25853"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2015.02.008"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/9.7.617"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0798-677"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220145110"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-056-X:1"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307764200"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(83)90173-6"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830151003"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-01-0039"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1248943"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002344"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08881-7"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-82841-w"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-018-2612-6"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-351932"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.207266"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-020-0292-7"},{"issue":"1","key":"e_1_2_7_80_1","article-title":"Potent preclinical efficacy of DuoHexaBody\u2010CD37 in B\u2010cell malignancies","volume":"5","author":"Horst HJ","year":"2021","journal-title":"Hema"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-740944"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-687749"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-3192"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.123"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005220"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.1.181"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(99)00147-2"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3180959e09"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2021.102284"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-703439"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104663"},{"key":"e_1_2_7_92_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-179504"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90404-2"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(94)90130-9"},{"key":"e_1_2_7_95_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053010"},{"key":"e_1_2_7_96_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-0323"},{"key":"e_1_2_7_97_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11040456"},{"key":"e_1_2_7_98_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80420"},{"key":"e_1_2_7_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.02.001"},{"key":"e_1_2_7_100_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-20-0044"},{"key":"e_1_2_7_101_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003731"},{"key":"e_1_2_7_102_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.21.13353"},{"key":"e_1_2_7_103_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101243"},{"key":"e_1_2_7_104_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1225704"},{"issue":"2","key":"e_1_2_7_105_1","article-title":"1070 HexaBody\u2010CD27 enhances T\u2010cell activation, proliferation, cytokine secretion and cytotoxic activity independently of Fc gamma receptor\u2010mediated crosslinking","volume":"10","author":"N\u00fcrmberger K","year":"2022","journal-title":"J Immunother Cancer"},{"issue":"1","key":"e_1_2_7_106_1","first-page":"A911","article-title":"813 combination of HexaBody\u2010CD27 with PD\u2010(L)1 blockade potentiates single\u2010agent activity leading to enhanced human T\u2010cell effector functions in\u00a0vitro","volume":"11","author":"Imle A","year":"2023","journal-title":"J Immunother Cancer"},{"issue":"2","key":"e_1_2_7_107_1","first-page":"A897","article-title":"856 INBRX\u2010106: a novel hexavalent anti\u2010OX40 agonist for the treatment of solid tumors","volume":"9","author":"Rowell E","year":"2021","journal-title":"J Immunother Cancer"},{"key":"e_1_2_7_108_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.957874"},{"key":"e_1_2_7_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01384-1"}],"container-title":["Immunological Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imr.13394","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imr.13394","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imr.13394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:42:11Z","timestamp":1786542131000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imr.13394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,14]]},"references-count":108,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/imr.13394"],"URL":"https:\/\/doi.org\/10.1111\/imr.13394","archive":["Portico"],"relation":{},"ISSN":["0105-2896","1600-065X"],"issn-type":[{"value":"0105-2896","type":"print"},{"value":"1600-065X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,14]]},"assertion":[{"value":"2024-09-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}