Harari-Steinfeld R, Abhinav Ayyadevara VSS, Cuevas L, et al. Standardized In-Vitro Evaluation of CAR-T Cells Using Acellular Artificial Target Particles. Frontiers in Immunology. 2022; (doi: 10.3389/fimmu.2022.994532).
Acellular artificial target particles (aaTPs) have emerged as a promising tool for the development and in vitro evaluation of chimeric antigen receptor (CAR) T cells that can successfully treat solid tumors. That goal has been elusive, due to the overexpression of heterogenous tumor-associated antigens and the highly immunosuppressive tumor microenvironments of solid tumors — which underscores the importance of understanding the activity, specificity, and potency of engineered cells prior to clinical application. Standard practices for both conventional and next-generation CAR T products currently employ model target cell lines for assaying, but the approach is not optimal. To create a more controlled and standardized technique, researchers built a biomaterial-based platform using magnetic microbeads already common in the CAR-T cell manufacturing process. The novel platform proved to be a simple, affordable, and easy-to-maintain construct for demonstrating the proposed mechanism of action of an experimental CAR-T product. Specifically, through co-incubation of aaTPs with CAR T cells followed by cytometry and cytokine assays, investigators successfully pinpointed the antigen-specific and dose-dependent activation of CAR T cells directed at human epidermal growth factor receptor 2 (HER2), a known therapeutic target protein expressed on many solid tumors.
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