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Background <p>MUC1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC), but MUC1-targeted CAR-NK cells remain unexplored in this malignancy.</p> Methods <p>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.</p> Results <p>MUC1 was expressed in 70% (63/90) of ESCC cases versus 14.9% (7/47) of adjacent normal tissues (<i>P</i> &lt; 0.001), with negligible expression in normal organs. Among MUC1-positive ESCCs, 88.9% and 42.8% showed &gt; 50% and &gt; 80% tumor cell positivity, respectively. iPSC-derived MUC1 CAR-NK cells exhibited &gt; 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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月18日

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

摘要

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.