Back to Search
Start Over
CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome
- Source :
- Science Advances. 8
- Publication Year :
- 2022
- Publisher :
- American Association for the Advancement of Science (AAAS), 2022.
-
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 CAR High T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CAR High 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.
- Subjects :
- Multidisciplinary
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Science Advances
- Accession number :
- edsair.doi.dedup.....9b4d5aef60ed3ce12d8e6ee7288a7dbd
- Full Text :
- https://doi.org/10.1126/sciadv.abo0514