Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth

Nat Commun. 2024 Jan 19;15(1):615. doi: 10.1038/s41467-024-44873-4.


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.

MeSH terms

  • Antibodies
  • B-Cell Maturation Antigen / genetics
  • CD24 Antigen
  • Humans
  • Multiple Myeloma* / pathology
  • Neoplasm Recurrence, Local
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes


  • Receptors, Chimeric Antigen
  • B-Cell Maturation Antigen
  • Antibodies
  • CD24 protein, human
  • CD24 Antigen