# name
CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome

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Fernández de Larrea Rodríguez, Carlos José

# metadata.dc.description.abstract[].value
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.

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American Association for the Advancement of Science

# metadata.dc.rights[].value
cc by-nc (c) Rodríguez Márquez, Paula et al, 2022

# metadata.dc.source[].value
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

# metadata.dc.title[].value
CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome