Document type
ArticleVersion
Published versionPublication date
Publication license
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/209150
CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome
Journal Title
Director/Tutor
Journal ISSN
Volume Title
Related resource
Abstract
Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study, we address the impact of CAR density on the functionality of BCMA CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with up-regulation of exhaustion markers and increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of gene regulatory networks using scRNA-seq identified regulons associated to activation and exhaustion up-regulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with notable impact on clinical response.
Subject
Subject (English)
Citation
Citation
RODRÍGUEZ MÁRQUEZ, Paula, et al. CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome. Science Advances. 2022. Vol. 8, num. 39. ISSN 2375-2548. [consulted: 12 of June of 2026]. Available at: https://hdl.handle.net/2445/209150