{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T07:36:06Z","timestamp":1780817766025,"version":"3.54.1"},"reference-count":31,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K08CA222704"],"award-info":[{"award-number":["K08CA222704"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Comprehensive Cancer Network Foundation","award":["K08CA222704"],"award-info":[{"award-number":["K08CA222704"]}]},{"name":"Paul Ohara II Seed Grant Award","award":["K08CA222704"],"award-info":[{"award-number":["K08CA222704"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>An antibody\u2013drug conjugate (ADC) targeting CD46 conjugated to monomethyl auristatin has a potent anti-myeloma effect in cell lines in vitro and in vivo, and patient samples treated ex vivo. Here, we tested if CD46\u2013ADC may have the potential to target MM-initiating cells (MM-ICs). CD46 expression was measured on primary MM cells with a stem-like phenotype. A patient-derived xenograft (PDX) model was implemented utilizing implanted fetal bone fragments to provide a humanized microenvironment. Engraftment was monitored via serum human light chain ELISA, and at sacrifice via bone marrow and bone fragment flow cytometry. We then tested MM regeneration in PDX by treating mice with CD46\u2013ADC or the nonbinding control\u2013ADC. MM progenitor cells from patients that exhibit high aldehyde dehydrogenase activity also have a high expression of CD46. In PDX, newly diagnosed MM patient samples engrafted significantly more compared to relapsed\/refractory samples. In mice transplanted with newly diagnosed samples, CD46\u2013ADC treatment showed significantly decreased engraftment compared to control\u2013ADC treatment. Our data further support the targeting of CD46 in MM. To our knowledge, this is the first study to show preclinical drug efficacy in a PDX model of MM. This is an important area for future study, as patient samples but not cell lines accurately represent intratumoral heterogeneity.<\/jats:p>","DOI":"10.3390\/cancers15225335","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T03:42:40Z","timestamp":1699501360000},"page":"5335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CD46\u2013ADC Reduces the Engraftment of Multiple Myeloma Patient-Derived Xenografts"],"prefix":"10.3390","volume":"15","author":[{"given":"Michael J.","family":"VanWyngarden","sequence":"first","affiliation":[{"name":"Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary J.","family":"Walker","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Perez de Acha","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett M.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Forsberg","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomer M.","family":"Mark","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-0964","authenticated-orcid":false,"given":"William","family":"Matsui","sequence":"additional","affiliation":[{"name":"Livestrong Cancer Institutes, Dell Medical School, University of Texas at Austin, Austin, TX 78705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Sherbenou","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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