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Dynamic Profiling of Antitumor Activity of CAR T Cells Using Micropatterned Tumor Arrays
Cancer immunotherapy based on the engineering of chimeric antigen receptors (CAR) on T cells has emerged as one of the most promising new therapies for patients with B‐cell malignancies. Preclinical assessments of essential CAR T cell functions such as trafficking and cytotoxicity are critical for accelerating the development of highly effective therapeutic candidates. However, current tools for evaluating CAR‐T functions lack sufficient precision. Here, a micropatterned tumor array (MiTA) is described that enables detailed and dynamic characterization of CAR T cell trafficking toward tumor‐cell islands and subsequent killing of tumor cells. It is shown that CAR T cells often merge into large clusters that envelop and kill the tumor cells with high efficiency. Significant differences are also measured between CAR T cells from different donors and between various CAR T cell constructs. Overall, the assay allows for multifaceted, dynamic, high‐content evaluation of CAR T trafficking, clustering, and killing and could eventually become a useful tool for immune‐oncology research and preclinical assessments of cell‐based immunotherapies.
Dynamic Profiling of Antitumor Activity of CAR T Cells Using Micropatterned Tumor Arrays
Cancer immunotherapy based on the engineering of chimeric antigen receptors (CAR) on T cells has emerged as one of the most promising new therapies for patients with B‐cell malignancies. Preclinical assessments of essential CAR T cell functions such as trafficking and cytotoxicity are critical for accelerating the development of highly effective therapeutic candidates. However, current tools for evaluating CAR‐T functions lack sufficient precision. Here, a micropatterned tumor array (MiTA) is described that enables detailed and dynamic characterization of CAR T cell trafficking toward tumor‐cell islands and subsequent killing of tumor cells. It is shown that CAR T cells often merge into large clusters that envelop and kill the tumor cells with high efficiency. Significant differences are also measured between CAR T cells from different donors and between various CAR T cell constructs. Overall, the assay allows for multifaceted, dynamic, high‐content evaluation of CAR T trafficking, clustering, and killing and could eventually become a useful tool for immune‐oncology research and preclinical assessments of cell‐based immunotherapies.
Dynamic Profiling of Antitumor Activity of CAR T Cells Using Micropatterned Tumor Arrays
Wang, Xiao (author) / Scarfò, Irene (author) / Schmidts, Andrea (author) / Toner, Mehmet (author) / Maus, Marcela V. (author) / Irimia, Daniel (author)
Advanced Science ; 6
2019-12-01
12 pages
Article (Journal)
Electronic Resource
English
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