| Autor: |
LaBelle, Cody A., Zhang, Raymond J., Hunsucker, Sally A., Armistead, Paul M., Allbritton, Nancy L. |
| Zdroj: |
Cytometry. Part A; Mar2023, Vol. 103 Issue 3, p208-220, 13p |
| Abstrakt: |
Chimeric antigen receptor T (CAR‐T) cell immunotherapies have seen success in treating hematological malignancies in recent years; however, the results can be highly variable. Single cell heterogeneity plays a key role in the variable efficacy of CAR‐T cell treatments yet is largely unexplored. A major challenge is to understand the killing behavior and phenotype of individual CAR‐T cells, which are able to serially kill targets. Thus, a platform capable of measuring time‐dependent CAR‐T cell mediated killing and then isolating single cells for downstream assays would be invaluable in characterizing CAR‐T cells. An automated microraft array platform was designed to track CD19 CAR‐T cell killing of CD19+ target cells and CAR‐T cell motility over time followed by CAR‐T cell collection based on killing behavior. The platform demonstrated automated CAR‐T cell counting with up to 98% specificity and 96% sensitivity, and single cells were isolated with 89% efficiency. On average, 2.3% of single CAR‐T cells were shown to participate in serial‐killing of target cells, killing a maximum of three target cells in a 6 h period. The cytotoxicity and motility of >7000 individual CAR‐T cells was tracked across four microraft arrays. The automated microraft array platform measured temporal cell‐mediated cytotoxicity, CAR‐T cell motility, CAR‐T cell death, and CAR‐T cell to target cell distances, followed by the capability to sort any desired CAR‐T cell. The pipeline has the potential to further our understanding of T cell‐based cancer immunotherapies and improve cell‐therapy products for better patient outcomes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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