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Preclinical efficacy of iPSC-derived MUC1-targeted CAR-NK cells against esophageal squamous cell carcinoma.

Created on 19 Jul 2026

Authors

Yuting Peng, Tian Guan, Yi Xiao, Shugeng Lin, Jijun Wu, Yan Lin, Juping Wang, Haoyu Zeng, Changchun Ma

Published in

Cancer immunology, immunotherapy : CII. Jul 18, 2026. Epub Jul 18, 2026.

Abstract

MUC1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC), but MUC1-targeted CAR-NK cells remain unexplored in this malignancy.
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.
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.
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.

PMID:
42471452
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.

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