학술논문
Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth.
Document Type
Academic Journal
Author
Sun F; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Cheng Y; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Wanchai V; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Guo W; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Mery D; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Xu H; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Gai D; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Siegel E; Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Bailey C; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Ashby C; Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Al Hadidi S; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Schinke C; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Thanendrarajan S; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Ma Y; iCell Gene Therapeutics LLC, Research & Development Division, Stony Brook, NY, 11790, USA.; Yi Q; Center for Translational Research in Hematologic Malignancies, Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston, TX, 77030, USA.; Orlowski RZ; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.; Zangari M; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; van Rhee F; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Janz S; Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.; Bishop G; Department of Microbiology and Immunology, University of Iowa and VA Medical Center, Iowa City, IA, 52242, USA.; Tricot G; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Shaughnessy JD Jr; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.; Zhan F; Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. FZhan@uams.edu.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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.
(© 2024. The Author(s).)
(© 2024. The Author(s).)