Journal
ANALYTICAL CHEMISTRY
Volume 93, Issue 4, Pages 2327-2335Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.0c04202
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Funding
- Canadian Institutes of Health Research [FDN-148415]
- Collaborative Health Research Projects program (CIHR/NSERC)
- University of Toronto's Medicine by Design initiative
- Canada First Research Excellence Fund
- Alexander Graham Bell Canada Graduate Scholarship
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CAR-QC is a novel microfluidic approach that can efficiently detect and robustly deplete rare leukemic B cells in therapeutic T cell samples. It offers ultrasensitive detection of leukemic B cells at single-cell resolution and robust depletion efficiency up to 99.985%, outperforming flow cytometry and magnetic-activated cell sorting. The improved performance of CAR-QC helps to avoid the occurrence and possible relapse of rare leukemic B cells in vitro.
Rare CD19(+) leukemic B cells present in purified T cell populations can cause disease relapse and even the failure of CD19-targeting CAR-T therapy as these rare cells have the ability to self-mask their surface CD19 and escape from the recognition of T cells. It is therefore critical to efficiently detect and robustly deplete rare leukemic B cells in samples of therapeutic T cells. Here, we present a novel microfluidic approach to address the challenges specific to quality control of therapeutic T cells - CAR-QC. CAR-QC utilizes immunomagnetic labeling with a highly selective microfluidic device to rank and isolate rare leukemic B cells in T cell populations. CAR-QC offers ultrasensitive detection of leukemic B cells at single-cell resolution and robust depletion efficiency up to 99.985%. We demonstrate that CAR-QC outperforms flow cytometry and magnetic-activated cell sorting for detecting or purifying spiked samples. In addition, we prove that the improved performance of CAR-QC helps to avoid the occurrence and possibly relapse of rare leukemic B cells in vitro.
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