Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma

• Published in: Frontiers in immunology Vol. 15; p. 1337557
• Main Authors: Lin, Xiaolan, Guan, Tian, Li, Yun, Lin, Yanchun, Huang, Guowei, Lin, Yan, Sun, Pingnan, Li, Congzhu, Gu, Jiang, Zeng, Haoyu, Ma, Changchun
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.02.2024
• Subjects: chimeric antigen receptor (CAR); Immunology; induced pluripotent stem (iPS) cell; iPSC-derived MUC1-targeted CAR-NK cells; mucin 1; NK cells therapy; oral tongue squamous cell carcinoma; chimeric antigen receptor (CAR); NK cells therapy; oral tongue squamous cell carcinoma; induced pluripotent stem (iPS) cell; mucin 1; iPSC-derived MUC1-targeted CAR-NK cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1337557

The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined. We assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively. MUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells , in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.