{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:47:15Z","timestamp":1776408435019,"version":"3.51.2"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,8,8]],"date-time":"2013-08-08T00:00:00Z","timestamp":1375920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2013,10]]},"abstract":"Summary<\/jats:title>The treatment of chronic lymphocytic leukaemia (CLL<\/jats:styled-content>) has been improved by introduction of monoclonal antibodies (mA<\/jats:styled-content>bs) that exert their effect through secondary effector mechanisms. CLL<\/jats:styled-content> cells are characterized by expression of CD<\/jats:styled-content>5 and CD<\/jats:styled-content>23 along with CD<\/jats:styled-content>19 and CD<\/jats:styled-content>20, hence anti\u2010CD<\/jats:styled-content>5 A<\/jats:styled-content>bs that engage secondary effector functions represent an attractive opportunity for CLL<\/jats:styled-content> treatment. Here, a repertoire of mA<\/jats:styled-content>bs against human CD<\/jats:styled-content>5 was generated and tested for ability to induce complement\u2010dependent cytotoxicity (CDC<\/jats:styled-content>) and antibody\u2010dependent cell\u2010mediated cytotoxicity (ADCC<\/jats:styled-content>) both as single mA<\/jats:styled-content>bs and combinations of two mA<\/jats:styled-content>bs against non\u2010overlapping epitopes on human CD<\/jats:styled-content>5. The results demonstrated that combinations of two mA<\/jats:styled-content>bs significantly increased the level of CDC<\/jats:styled-content> compared to the single mA<\/jats:styled-content>bs, while no enhancement of ADCC<\/jats:styled-content> was seen with anti\u2010CD<\/jats:styled-content>5 mA<\/jats:styled-content>b combinations. High levels of CDC<\/jats:styled-content> and ADCC<\/jats:styled-content> correlated with low levels of A<\/jats:styled-content>b\u2010induced CD<\/jats:styled-content>5 internalization and degradation. Importantly, an anti\u2010CD<\/jats:styled-content>5 mA<\/jats:styled-content>b combination enhanced CDC<\/jats:styled-content> of CLL<\/jats:styled-content> cells when combined with the anti\u2010CD<\/jats:styled-content>20 mA<\/jats:styled-content>bs rituximab and ofatumumab as well as with the anti\u2010CD<\/jats:styled-content>52 mA<\/jats:styled-content>b alemtuzumab. These results suggest that an anti\u2010CD<\/jats:styled-content>5 mA<\/jats:styled-content>b combination inducing CDC<\/jats:styled-content> and ADCC<\/jats:styled-content> may be effective alone, in combination with mA<\/jats:styled-content>bs against other targets or combined with chemotherapy for CLL<\/jats:styled-content> and other CD<\/jats:styled-content>5\u2010expressing haematological or lymphoid malignancies.<\/jats:p>","DOI":"10.1111\/bjh.12503","type":"journal-article","created":{"date-parts":[[2013,8,8]],"date-time":"2013-08-08T13:04:58Z","timestamp":1375967098000},"page":"182-193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Combination of two anti\u2010CD<\/scp>5 monoclonal antibodies synergistically induces complement\u2010dependent cytotoxicity of chronic lymphocytic leukaemia cells"],"prefix":"10.1111","volume":"163","author":[{"given":"Josephine L.","family":"Klitgaard","sequence":"first","affiliation":[{"name":"Symphogen A\/S Lyngby Denmark"},{"name":"Department of Haematology L4042 Rigshospitalet Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Koefoed","sequence":"additional","affiliation":[{"name":"Symphogen A\/S Lyngby Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Geisler","sequence":"additional","affiliation":[{"name":"Department of Haematology L4042 Rigshospitalet Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole V.","family":"Gadeberg","sequence":"additional","affiliation":[{"name":"Department of Haematology Vejle Sygehus Vejle Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Boston MA USA"},{"name":"Department of Medicine Harvard Medical School Boston MA USA"},{"name":"Brigham and Women's Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f8rgen","family":"Petersen","sequence":"additional","affiliation":[{"name":"Symphogen A\/S Lyngby Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper","family":"Jurlander","sequence":"additional","affiliation":[{"name":"Department of Haematology L4042 Rigshospitalet Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikkel W.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Symphogen A\/S Lyngby Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-010-9353-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/10.8.1185"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.1999.540102.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-111781"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6226"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1984.2.8.881"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt832"},{"key":"e_1_2_8_9_1","first-page":"405","article-title":"Synergistic cytotoxic effects of antibodies directed against different cell surface determinants","volume":"34","author":"Elliott E.V.","year":"1978","journal-title":"Immunology"},{"key":"e_1_2_8_10_1","first-page":"2691","article-title":"Phase I study of the pharmacokinetics of a radioimmunoconjugate, 90Y\u2010T101, in patients with CD5\u2010expressing leukemia and lymphoma","volume":"4","author":"Foss F.M.","year":"1998","journal-title":"Clinical Cancer Research"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.02.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0647"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.12.3383"},{"key":"e_1_2_8_14_1","unstructured":"S. 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