Dynamic Profiling of Antitumor Activity of CAR T Cells Using Micropatterned Tumor Arrays

Abstract

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.

Microfluidic techniques for isolation, formation, and characterization of circulating tumor cells and clusters

“…5(e) ]. Wang et al 116 created a micropatterned tumor array, which described enabled detailed and dynamic characterization of CAR T cell trafficking toward tumor cell islands and targeting of tumor cells. Their assay allowed for the assessment of CAR T trafficking for immune-oncology research and preclinical assessments of cell-based immunotherapies.…”

“…Their assay allowed for the assessment of CAR T trafficking for immune-oncology research and preclinical assessments of cell-based immunotherapies. 116 Khoo et al 93 evaluated drug response of patient-derived CTCs of breast cancer patients throughout the time of treatment using their microwell system [ Fig. 5(f) ].…”

Nanotechnology Promotes Genetic and Functional Modifications of Therapeutic T Cells Against Cancer

“…Microtechologies such as chromium (Cr‐51) release assay, quantification of cytosolic enzymes (e.g., lactose dehydrogenase (LDH)), time‐lapse imaging, electrical impedance sensors, and micropatterning were used to measure and monitor CAR‐T cell cytotoxicity. [ 133 ]…”

Harnessing the potential of CRISPR-based platforms to advance the field of hospital medicine

“…Recently, investigators treated a patient with aggressive lung cancer with T-cells edited by CRISPR [75]. Clinical trials the safety and efficacy of CAR T-cell immunotherapy for leukemia and lymphoma are ongoing and may soon expand to solid organ malignancies [74,76,77].…”