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• W3049456218 abstract "The tumoricidal efficiency of human CAR-T cells is generally evaluated using immune-deficient mouse models; however, due to their immune-incompetency and the species-specific reactivity of a target antigen, these models are problematic to imitate CAR-T-induced adverse effects in the clinic. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen overtly presented on the cell surface of various carcinomas, making it an attractive target for CAR-T therapy. Here, we developed an anti-mouse EpCAM CAR to evaluate its safety and efficacy in immunocompetent mouse models. As previously reported for their human equivalents, murine EpCAM CAR-T cells exhibit promising anti-tumor efficacy in vitro and in vivo. However, after CAR-T infusion, various dose-depended toxicities including body weight loss, cytokine-release syndrome (CRS), and death were observed in both tumor-bearing and tumor-free mice. Pathological examination revealed unexpected and severe pulmonary immunopathology due to basal EpCAM expression in normal lung. While our study validates EpCAM CAR-T’s potent anti-tumor efficacy, it also reveals that EpCAM CAR-T cells used for the treatment of solid tumors may cause lethal toxicity and should, therefore, be evaluated in patients with caution." @default.
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• W3049456218 date "2020-01-01" @default.
• W3049456218 modified "2023-09-23" @default.
• W3049456218 title "Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models" @default.
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• W3049456218 doi "https://doi.org/10.1080/2162402x.2020.1806009" @default.
• W3049456218 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7458607" @default.
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• W3049456218 hasPublicationYear "2020" @default.
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