{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:40:48Z","timestamp":1781012448659,"version":"3.54.1"},"reference-count":60,"publisher":"American Society of Hematology","issue":"16","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Antibody-drug conjugates directed against tumor-specific targets have allowed targeted delivery of highly potent chemotherapy to malignant cells while sparing normal cells. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein with limited expression on normal adult tissues and is overexpressed on the surface of malignant cells in mantle cell lymphoma, acute lymphocytic leukemia with t(1;19)(q23;p13) translocation, and chronic lymphocytic leukemia. This differential expression makes ROR1 an attractive target for antibody-drug conjugate therapy, especially in malignancies such as mantle cell lymphoma and acute lymphocytic leukemia, in which systemic chemotherapy remains the gold standard. Several preclinical and phase 1 clinical studies have established the safety and effectiveness of anti-ROR1 monoclonal antibody\u2013based therapies. Herein we describe a humanized, first-in-class anti-ROR1 antibody-drug conjugate, huXBR1-402-G5-PNU, which links a novel anti-ROR1 antibody (huXBR1-402) to a highly potent anthracycline derivative (PNU). We found that huXBR1-402-G5-PNU is cytotoxic to proliferating ROR1+ malignant cells in vitro and suppressed leukemia proliferation and extended survival in multiple models of mice engrafted with human ROR1+ leukemia. Lastly, we show that the B-cell lymphoma 2 (BCL2)-dependent cytotoxicity of huXBR1-402-G5-PNU can be leveraged by combined treatment strategies with the BCL2 inhibitor venetoclax. Together, our data present compelling preclinical evidence for the efficacy of huXBR1-402-G5-PNU in treating ROR1+ hematologic malignancies.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003276","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T15:38:15Z","timestamp":1629473895000},"page":"3152-3162","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":30,"title":["The ROR1 antibody-drug conjugate huXBR1-402-G5-PNU effectively targets ROR1+ leukemia"],"prefix":"10.1182","volume":"5","author":[{"given":"Eileen Y.","family":"Hu","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"},{"name":"Medical Scientist Training Program, The Ohio State University, Columbus, OH, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Emory University, Atlanta, GA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swagata","family":"Goswami","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Nunes","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-ling","family":"Chiang","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-9891","authenticated-orcid":false,"given":"Sara","family":"Elgamal","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Ventura","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Cheney","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevan","family":"Zapolnik","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Williams","sequence":"additional","affiliation":[{"name":"Flow Cytometry Core, Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeswaran","family":"Mani","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Frissora","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokui","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, The Ohio State University, Columbus, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Waldmeier","sequence":"additional","affiliation":[{"name":"NBE-Therapeutics Ltd., Basel, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger R.","family":"Beerli","sequence":"additional","affiliation":[{"name":"NBE-Therapeutics Ltd., Basel, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9955-3454","authenticated-orcid":false,"given":"Christoph","family":"Rader","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixiao","family":"Long","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Grawunder","sequence":"additional","affiliation":[{"name":"NBE-Therapeutics Ltd., Basel, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natarajan","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"issue":"5","key":"2021082015375639800_B1","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1158\/1078-0432.CCR-07-1255","article-title":"Acquired resistance to rituximab is associated with 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