Cancer immunology, immunotherapy : CII · 2026
Preclinical efficacy of iPSC-derived MUC1-targeted CAR-NK cells against esophageal squamous cell carcinoma.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Peng Yuting, Guan Tian, Xiao Yi, Lin Shugeng, Wu Jijun, Lin Yan, Wang Juping, Zeng Haoyu, Ma Changchun
Аннотация
BACKGROUND: MUC1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC), but MUC1-targeted CAR-NK cells remain unexplored in this malignancy.
METHODS: MUC1 expression was assessed by IHC in 90 ESCC specimens, 47 paired adjacent normal tissues, and normal human organs. MUC1-targeted CAR-NK cells were generated from an iPSC platform. Antitumor activity was evaluated against patient-specific ESCC organoids (PSOs), primary ESCC cells, KYSE150 and KYSE140 cells using live/dead staining, CCK-8, and xCELLigence assays. In vivo efficacy was assessed in a KYSE140 xenograft model.
RESULTS: MUC1 was expressed in 70% (63/90) of ESCC cases versus 14.9% (7/47) of adjacent normal tissues (P < 0.001), with negligible expression in normal organs. Among MUC1-positive ESCCs, 88.9% and 42.8% showed > 50% and > 80% tumor cell positivity, respectively. iPSC-derived MUC1 CAR-NK cells exhibited > 95% CAR expression across iPSC, progenitor, and mature stages. Compared with controls, MUC1 CAR-NK cells elicited potent, antigen-specific cytotoxicity against MUC1-expressing ESCC PSOs, primary cells, KYSE150, and KYSE140 in vitro and significantly suppressed KYSE140 xenograft growth in vivo.
CONCLUSION: iPSC-derived MUC1-targeted CAR-NK cells exert robust and specific antitumor efficacy against human ESCC, supporting clinical translation of this off-the-shelf cell therapy.
METHODS: MUC1 expression was assessed by IHC in 90 ESCC specimens, 47 paired adjacent normal tissues, and normal human organs. MUC1-targeted CAR-NK cells were generated from an iPSC platform. Antitumor activity was evaluated against patient-specific ESCC organoids (PSOs), primary ESCC cells, KYSE150 and KYSE140 cells using live/dead staining, CCK-8, and xCELLigence assays. In vivo efficacy was assessed in a KYSE140 xenograft model.
RESULTS: MUC1 was expressed in 70% (63/90) of ESCC cases versus 14.9% (7/47) of adjacent normal tissues (P < 0.001), with negligible expression in normal organs. Among MUC1-positive ESCCs, 88.9% and 42.8% showed > 50% and > 80% tumor cell positivity, respectively. iPSC-derived MUC1 CAR-NK cells exhibited > 95% CAR expression across iPSC, progenitor, and mature stages. Compared with controls, MUC1 CAR-NK cells elicited potent, antigen-specific cytotoxicity against MUC1-expressing ESCC PSOs, primary cells, KYSE150, and KYSE140 in vitro and significantly suppressed KYSE140 xenograft growth in vivo.
CONCLUSION: iPSC-derived MUC1-targeted CAR-NK cells exert robust and specific antitumor efficacy against human ESCC, supporting clinical translation of this off-the-shelf cell therapy.