Journal article
Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth
Nature communications, Vol.15(1), 615
01/19/2024
DOI: 10.1038/s41467-024-44873-4
PMCID: PMC10798961
PMID: 38242888
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.
Details
- Title: Subtitle
- Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth
- Creators
- Fumou Sun - Winthrop Rockefeller FoundationYan Cheng - Winthrop Rockefeller FoundationVisanu Wanchai - University of Arkansas for Medical SciencesWancheng Guo - Winthrop Rockefeller FoundationDavid Mery - Winthrop Rockefeller FoundationHongwei Xu - University of Arkansas for Medical SciencesDongzheng Gai - University of Arkansas for Medical SciencesEric Siegel - University of Arkansas for Medical SciencesClyde Bailey - Winthrop Rockefeller FoundationCody Ashby - University of Arkansas for Medical SciencesSamer Al Hadidi - University of Arkansas for Medical SciencesCarolina Schinke - Winthrop Rockefeller FoundationSharmilan Thanendrarajan - Winthrop Rockefeller FoundationYupo Ma - iCell Gene Therapeutics LLC, Research & Development Division, Stony Brook, NY, 11790, USAQing Yi - Houston MethodistRobert Z Orlowski - The University of Texas MD Anderson Cancer CenterMaurizio Zangari - University of Arkansas for Medical SciencesFrits van Rhee - University of Arkansas for Medical SciencesSiegfried Janz - Medical College of WisconsinGail Bishop - Iowa City VA Medical CenterGuido Tricot - Winthrop Rockefeller FoundationJohn D Shaughnessy Jr - University of Arkansas for Medical SciencesFenghuang Zhan - Winthrop Rockefeller Foundation
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.15(1), 615
- DOI
- 10.1038/s41467-024-44873-4
- PMID
- 38242888
- PMCID
- PMC10798961
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- U54 CA272691 / NCI NIH HHS R01 CA236814 / NCI NIH HHS
- Language
- English
- Date published
- 01/19/2024
- Academic Unit
- Microbiology and Immunology; President; Pathology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984548479802771
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