{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T09:16:04Z","timestamp":1778318164075,"version":"3.51.4"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":70,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"publisher","award":["DR3-06924"],"award-info":[{"award-number":["DR3-06924"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UCSD Foundation Blood Cancer Research Fund","award":["R01-CA236361"],"award-info":[{"award-number":["R01-CA236361"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005968","name":"Leukemia Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tower Cancer Research Foundation Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is selectively expressed on chronic lymphocytic leukemia (CLL) B cells and certain cancers, but is absent from normal B cells and healthy adult tissues. GE-zilovertamab, an afucosylated anti-ROR1 IgG1 antibody, is engineered to increase Fc\u03b3RIIIA binding and thereby enhance antibody-dependent cellular cytotoxicity (ADCC). Co-culture assays were performed using CLL cell lines (MEC1, MEC1-ROR1) and primary CLL cells with Jurkat-Lucia\u2122 NFAT-CD16, NK, or peripheral blood mononuclear cell effectors. Treatments included the anti-CD20 mAb rituximab, anti-ROR1 mAbs (GE-zilovertamab, zilovertamab), and the endocytosis inhibitor prochlorperazine, and ADCC was quantified. GE-zilovertamab showed significantly higher ADCC than its parental antibody and activity that was comparable to that of rituximab. We find that the endocytosis inhibitor prochlorperazine further increased this effect. GE-zilovertamab is a promising next-generation immunotherapeutic for CLL, combining selective targeting of ROR1 with the potential to reduce therapy-induced immunodeficiency compared with anti-CD20 antibodies.<\/jats:p>\n                  <jats:p>Statement of Significance An afucosylated anti-receptor tyrosine kinase-like orphan receptor 1 antibody potently kills receptor tyrosine kinase-like orphan receptor 1-expressing leukemic B cells while sparing normal B cells, and this selective cytotoxicity is further enhanced by prochlorperazine. This combination has the potential to advance leukemia immunotherapy by targeting malignant cells while preserving humoral immunity, thereby addressing infection risks associated with anti-CD20 antibody regimens.<\/jats:p>","DOI":"10.1093\/abt\/tbag001","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:04:43Z","timestamp":1768478683000},"page":"70-75","source":"Crossref","is-referenced-by-count":0,"title":["A glycoengineered anti-ROR1 antibody, GE-zilovertamab, selectively enhances antibody-dependent cellular cytotoxicity against chronic lymphocytic leukemia"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1271-4428","authenticated-orcid":false,"given":"Md Kamrul","family":"Hasan","sequence":"first","affiliation":[{"name":"Center for Novel Therapeutics, Moores Cancer Center, University of California San Diego , 9310 Athena Circle, La Jolla, CA 92037-0809,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Widhopf II","sequence":"additional","affiliation":[{"name":"Center for Novel Therapeutics, Moores Cancer Center, University of California San Diego , 9310 Athena Circle, La Jolla, CA 92037-0809,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J","family":"Kipps","sequence":"additional","affiliation":[{"name":"Center for Novel Therapeutics, Moores Cancer Center, University of California San Diego , 9310 Athena Circle, La Jolla, CA 92037-0809,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"2026050904364218200_ref1","doi-asserted-by":"publisher","first-page":"16096","DOI":"10.1038\/nrdp.2016.96","article-title":"Chronic lymphocytic leukaemia","volume":"3","author":"Kipps","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2026050904364218200_ref2","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s41408-022-00756-9","article-title":"Chronic lymphocytic leukemia treatment algorithm 2022","volume":"12","author":"Hampel","year":"2022","journal-title":"Blood Cancer J"},{"key":"2026050904364218200_ref3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3390\/life13061272","article-title":"Risk of infections secondary to the use of targeted therapies in hematological malignancies","author":"Andreescu","year":"2023","journal-title":"Life (Basel)"},{"key":"2026050904364218200_ref4","doi-asserted-by":"publisher","first-page":"e357","DOI":"10.1093\/oncolo\/oyac032","article-title":"Impact of therapy in patients with hematologic malignancies on seroconversion rates after SARS-CoV-2 vaccination","volume":"27","author":"Guven","year":"2022","journal-title":"Oncologist."},{"key":"2026050904364218200_ref5","doi-asserted-by":"publisher","first-page":"989830","DOI":"10.3389\/fphar.2022.989830","article-title":"Targeted therapies in CLL\/SLL and the cumulative incidence of infection: a systematic review and meta-analysis","volume":"13","author":"Vassilopoulos","year":"2022","journal-title":"Front Pharmacol"},{"key":"2026050904364218200_ref6","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.htct.2023.05.006","article-title":"Infections in patients with chronic lymphocytic leukemia","volume":"45","author":"Guarana","year":"2023","journal-title":"Hematol Transfus Cell Ther"},{"key":"2026050904364218200_ref7","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1182\/blood.2021014760","article-title":"ROR1: an orphan becomes apparent","volume":"140","author":"Kipps","year":"2022","journal-title":"Blood."},{"key":"2026050904364218200_ref8","doi-asserted-by":"publisher","first-page":"e953","DOI":"10.1016\/j.stem.2018.05.018","article-title":"Phase I trial: cirmtuzumab inhibits ROR1 signaling and stemness signatures in patients with chronic lymphocytic leukemia","volume":"22","author":"Choi","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2026050904364218200_ref9","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1136\/jcp.51.5.364","article-title":"Levels of expression of CD19 and CD20 in chronic B cell leukaemias","volume":"51","author":"Ginaldi","year":"1998","journal-title":"J Clin Pathol"},{"key":"2026050904364218200_ref10","doi-asserted-by":"publisher","first-page":"10731","DOI":"10.1073\/pnas.1708264114","article-title":"MicroRNA dysregulation to identify therapeutic target combinations for chronic lymphocytic leukemia","volume":"114","author":"Rassenti","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026050904364218200_ref11","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1093\/abt\/tby002","article-title":"Enhancing antibody-dependent cell-mediated cytotoxicity: a strategy for improving antibody-based immunotherapy","volume":"1","author":"Zahavi","year":"2018","journal-title":"Antib Ther"},{"key":"2026050904364218200_ref12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1136\/jitc-2020-002026","article-title":"Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia","author":"Caracciolo","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026050904364218200_ref13","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/cells12182312","article-title":"The chemical inhibitors of endocytosis: from mechanisms to potential clinical applications","author":"Szewczyk-Roszczenko","year":"2023","journal-title":"Cells."},{"key":"2026050904364218200_ref14","doi-asserted-by":"publisher","first-page":"e0121788","DOI":"10.1371\/journal.pone.0121788","article-title":"Identification of an ADAM17 cleavage region in human CD16 (FcgammaRIII) and the engineering of a non-cleavable version of the receptor in NK cells","volume":"10","author":"Jing","year":"2015","journal-title":"PLoS ONE"},{"key":"2026050904364218200_ref15","doi-asserted-by":"publisher","first-page":"e827","DOI":"10.1016\/j.cell.2020.02.019","article-title":"Endocytosis inhibition in humans to improve responses to ADCC-mediating antibodies","volume":"180","author":"Chew","year":"2020","journal-title":"Cell."},{"key":"2026050904364218200_ref16","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1182\/blood.2021015014","article-title":"Enduring undetectable MRD and updated outcomes in relapsed\/refractory CLL after fixed-duration venetoclax-rituximab","volume":"140","author":"Seymour","year":"2022","journal-title":"Blood."},{"key":"2026050904364218200_ref17","doi-asserted-by":"publisher","first-page":"9775","DOI":"10.1038\/s41598-023-36279-x","article-title":"Efficacy and safety of add-on anti-CD20 monoclonal antibody to Bruton tyrosine kinase inhibitor treatment for chronic lymphocytic leukemia: a meta-analysis","volume":"13","author":"Nguyen","year":"2023","journal-title":"Sci Rep"},{"key":"2026050904364218200_ref18","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s12308-020-00417-5","article-title":"Risk factors for hypogammaglobulinemia in chronic lymphocytic leukemia patients treated with anti-CD20 monoclonal antibody-based therapies","volume":"13","author":"McNulty","year":"2020","journal-title":"J Hematop"},{"key":"2026050904364218200_ref19","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1182\/bloodadvances.2022008445","article-title":"Analysis of immune responses in patients with CLL after heterologous COVID-19 vaccination","volume":"7","author":"Lee","year":"2023","journal-title":"Blood Adv"},{"key":"2026050904364218200_ref20","doi-asserted-by":"publisher","first-page":"EVIDoa2100001","DOI":"10.1056\/EVIDoa2100001","article-title":"Zilovertamab Vedotin targeting of ROR1 as therapy for lymphoid cancers","volume":"1","author":"Wang","year":"2022","journal-title":"NEJM Evid"}],"container-title":["Antibody Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/abt\/advance-article-pdf\/doi\/10.1093\/abt\/tbag001\/66420651\/tbag001.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/abt\/article-pdf\/9\/1\/70\/67314416\/tbag001.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/abt\/article-pdf\/9\/1\/70\/67314416\/tbag001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:36:47Z","timestamp":1778315807000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/abt\/article\/9\/1\/70\/8426266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,14]]}},"URL":"https:\/\/doi.org\/10.1093\/abt\/tbag001","relation":{},"ISSN":["2516-4236"],"issn-type":[{"value":"2516-4236","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2026,1]]}}}