Authors
Christopher M Smith, Ben Watts, Kathryn Evans, Hansen Kosasih, Chelsea Mayoh, Stephen W Erickson, Eric J Earley, Steven Neuhauser, Timothy M Stearns, Vivek M Philip, Jeffrey H Chuang, Charles E de Bock, Edward P Bowman, Katti A Jessen, Emily L Jocoy, Carol J Bult, Beverly A Teicher, Malcolm A Smith, Richard B Lock
Published in
HemaSphere. Volume 10. Issue 7. Pages e70438. Epub Jul 22, 2026.
Abstract
Although survival rates for acute lymphoblastic leukemia (ALL) have improved dramatically over the past 60 years, outcomes vary across different molecular subtypes and risk categories, and a significant number of patients remain difficult to treat. ROR1 is a receptor tyrosine kinase expressed in B-cell ALL, particularly in patients with TCF3::PBX1 gene rearrangements. ROR1 has served as the target of several immune-based therapies including antibody-drug conjugates (ADCs), bispecific T-cell engagers, and CAR T-cell therapies. Here, we evaluated the ROR1-targeting ADCs zilovertamab vedotin (ZV, previously known as MK-2140 or VLS-101) and VLS-211 in vivo against a panel of ALL patient-derived xenografts with variable ROR1 expression. Both agents showed modest activity, which was dependent on ROR1 expression. Notably, we identified pediatric patients with TCF3::HLF gene fusions, which is a highly chemoresistant ALL subtype, as having some of the highest ROR1 expression in pediatric ALL and show that this subtype is susceptible to targeting ROR1 via ADC-based therapy. Given that ZV has a favorable toxicity profile in patients with hematological malignancies, it may have some utility in the treatment of very high-risk pediatric B-ALL, particularly cases with TCF3::HLF gene fusions.
PMID:
42488471
Bibliographic data and abstract were imported from PubMed on 23 Jul 2026.
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