Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma
IntroductionThe 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....
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| 语言: | English |
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Frontiers Media S.A.
2024-02-01
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| 丛编: | Frontiers in Immunology |
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| 在线阅读: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1337557/full |
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| author | Xiaolan Lin Tian Guan Tian Guan Yun Li Yun Li Yanchun Lin Yanchun Lin Guowei Huang Yan Lin Pingnan Sun Congzhu Li Jiang Gu Haoyu Zeng Haoyu Zeng Haoyu Zeng Haoyu Zeng Changchun Ma Changchun Ma Changchun Ma Changchun Ma |
| author_facet | Xiaolan Lin Tian Guan Tian Guan Yun Li Yun Li Yanchun Lin Yanchun Lin Guowei Huang Yan Lin Pingnan Sun Congzhu Li Jiang Gu Haoyu Zeng Haoyu Zeng Haoyu Zeng Haoyu Zeng Changchun Ma Changchun Ma Changchun Ma Changchun Ma |
| author_sort | Xiaolan Lin |
| collection | DOAJ |
| description | IntroductionThe 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. MethodsWe 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 in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo 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.ResultsMUC1 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 vitro, 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. ConclusionThe MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials. |
| first_indexed | 2024-03-08T04:45:33Z |
| format | Article |
| id | doaj.art-2f4acbd60e284a1682c5172ca3fe7a7d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T04:45:33Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-2f4acbd60e284a1682c5172ca3fe7a7d2024-02-08T08:51:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13375571337557Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinomaXiaolan Lin0Tian Guan1Tian Guan2Yun Li3Yun Li4Yanchun Lin5Yanchun Lin6Guowei Huang7Yan Lin8Pingnan Sun9Congzhu Li10Jiang Gu11Haoyu Zeng12Haoyu Zeng13Haoyu Zeng14Haoyu Zeng15Changchun Ma16Changchun Ma17Changchun Ma18Changchun Ma19Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaGuangdong Procapzoom Bioscience Inc., Guangzhou, ChinaProcapzoom - Shantou University Medical College induced pluripotent stem cell (iPS) Research Center, Shantou, Guangdong, ChinaGuangdong Procapzoom Bioscience Inc., Guangzhou, ChinaProcapzoom - Shantou University Medical College induced pluripotent stem cell (iPS) Research Center, Shantou, Guangdong, ChinaGuangdong Procapzoom Bioscience Inc., Guangzhou, ChinaProcapzoom - Shantou University Medical College induced pluripotent stem cell (iPS) Research Center, Shantou, Guangdong, ChinaGuangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Medical Imaging, the Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Stem Cell Research Center, Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Gynecological Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaGuangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, ChinaGuangdong Procapzoom Bioscience Inc., Guangzhou, ChinaProcapzoom - Shantou University Medical College induced pluripotent stem cell (iPS) Research Center, Shantou, Guangdong, ChinaKey Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaProcapzoom - Shantou University Medical College induced pluripotent stem cell (iPS) Research Center, Shantou, Guangdong, ChinaGuangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, China0Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaIntroductionThe 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. MethodsWe 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 in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo 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.ResultsMUC1 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 vitro, 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. ConclusionThe MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1337557/fulliPSC-derived MUC1-targeted CAR-NK cellsoral tongue squamous cell carcinomamucin 1chimeric antigen receptor (CAR)induced pluripotent stem (iPS) cellNK cells therapy |
| spellingShingle | Xiaolan Lin Tian Guan Tian Guan Yun Li Yun Li Yanchun Lin Yanchun Lin Guowei Huang Yan Lin Pingnan Sun Congzhu Li Jiang Gu Haoyu Zeng Haoyu Zeng Haoyu Zeng Haoyu Zeng Changchun Ma Changchun Ma Changchun Ma Changchun Ma Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma Frontiers in Immunology iPSC-derived MUC1-targeted CAR-NK cells oral tongue squamous cell carcinoma mucin 1 chimeric antigen receptor (CAR) induced pluripotent stem (iPS) cell NK cells therapy |
| title | Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma |
| title_full | Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma |
| title_fullStr | Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma |
| title_full_unstemmed | Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma |
| title_short | Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma |
| title_sort | efficacy of muc1 targeted car nk cells against human tongue squamous cell carcinoma |
| topic | iPSC-derived MUC1-targeted CAR-NK cells oral tongue squamous cell carcinoma mucin 1 chimeric antigen receptor (CAR) induced pluripotent stem (iPS) cell NK cells therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1337557/full |
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