Faculty, Staff and Student Publications
Publication Date
1-19-2024
Journal
Nature Communications
Abstract
Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse. Residual myeloma cells following BCMA-CAR-T-mediated treatment show less-differentiated features and express stem-like genes, including CD24. CD24-positive myeloma cells represent a large fraction of residual myeloma cells after BCMA-CAR-T therapy. In this work, we develop CD24-CAR-T cells and test their ability to eliminate myeloma cells. We find that CD24-CAR-T cells block the CD24-Siglec-10 pathway, thereby enhancing macrophage phagocytic clearance of myeloma cells. Additionally, CD24-CAR-T cells polarize macrophages to a M1-like phenotype. A dual-targeted BCMA-CD24-CAR-T exhibits improved efficacy compared to monospecific BCMA-CAR-T-cell therapy. This work presents an immunotherapeutic approach that targets myeloma cells and promotes tumor cell clearance by macrophages.
Keywords
Humans, Receptors, Chimeric Antigen, Multiple Myeloma, T-Lymphocytes, B-Cell Maturation Antigen, Neoplasm Recurrence, Local, Antibodies, CD24 Antigen
DOI
10.1038/s41467-024-44873-4
PMID
38242888
PMCID
PMC10798961
PubMedCentral® Posted Date
January 2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Bioinformatics Commons, Biomedical Informatics Commons, Medical Biochemistry Commons, Oncology Commons
Comments
Supplementary Material
Data Availability Statement
PMID: 38242888