Faculty, Staff and Student Publications
Language
English
Publication Date
11-9-2023
Journal
Cancers
DOI
10.3390/cancers15225335
PMID
38001595
PMCID
PMC10670432
PubMedCentral® Posted Date
11-9-2023
PubMedCentral® Full Text Version
Post-print
Abstract
An antibody-drug 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-ADC 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-ADC or the nonbinding control-ADC. 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-ADC treatment showed significantly decreased engraftment compared to control-ADC 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.
Keywords
multiple myeloma, patient-derived xenografts, CD46, antibody–drug conjugate, multiple myeloma-initiating cells
Published Open-Access
yes
Recommended Citation
VanWyngarden, Michael J; Walker, Zachary J; Su, Yang; et al., "CD46-ADC Reduces the Engraftment of Multiple Myeloma Patient-Derived Xenografts" (2023). Faculty, Staff and Student Publications. 6211.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6211
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