Pluripotent stem cell-derived chimeric antigen receptor-natural killer cells targeting epidermal growth factor receptor 2 for cancer immunotherapy
Chimeric antigen receptor-natural killer (CAR-NK) cells are emerging as a promising platform for allogeneic, cell-based immunotherapy. Among available sources, NK cells derived from pluripotent stem cells (PSCs) provide a renewable and scalable option that overcomes the limitations of primary NK cel...
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| Vydáno v: | BMB reports Ročník 58; číslo 11; s. 475 |
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| Hlavní autoři: | , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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Korea (South)
01.11.2025
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| ISSN: | 1976-670X, 1976-670X |
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| Abstract | Chimeric antigen receptor-natural killer (CAR-NK) cells are emerging as a promising platform for allogeneic, cell-based immunotherapy. Among available sources, NK cells derived from pluripotent stem cells (PSCs) provide a renewable and scalable option that overcomes the limitations of primary NK cells. Human epidermal growth factor receptor 2 (HER2), a membrane protein frequently overexpressed in many solid tumors, is an attractive target for cancer immunotherapy. In this study, we designed a green fluorescent protein (GFP)-linked anti-HER2 CAR construct and introduced it into PSCs via lentiviral transduction. Three stable PSC-derived clones (CAR-A, CAR-B, and CAR-C) were established, each co-expressing anti-HER2 CAR with GFP. After differentiation under xeno-free and feeder-free culture conditions, CAR expression was maintained in NK cells. The resulting PSC-derived CAR-NK cells displayed phenotypic and functional features comparable to wild-type PSC-derived NK cells, while showing markedly enhanced cytotoxicity against HER2-positive cancer cell lines. These findings demonstrated the potential of the use of PSC-derived anti-HER2 CAR-NK cells as a robust and scalable immunotherapy. In addition, this platform could be extended to produce CAR-NK cells directed against a wide range of tumorassociated antigens. [BMB Reports 2025; 58(11): 475-483]. |
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| AbstractList | Chimeric antigen receptor-natural killer (CAR-NK) cells are emerging as a promising platform for allogeneic, cell-based immunotherapy. Among available sources, NK cells derived from pluripotent stem cells (PSCs) provide a renewable and scalable option that overcomes the limitations of primary NK cells. Human epidermal growth factor receptor 2 (HER2), a membrane protein frequently overexpressed in many solid tumors, is an attractive target for cancer immunotherapy. In this study, we designed a green fluorescent protein (GFP)-linked anti-HER2 CAR construct and introduced it into PSCs via lentiviral transduction. Three stable PSC-derived clones (CAR-A, CAR-B, and CAR-C) were established, each co-expressing anti-HER2 CAR with GFP. After differentiation under xeno-free and feeder-free culture conditions, CAR expression was maintained in NK cells. The resulting PSC-derived CAR-NK cells displayed phenotypic and functional features comparable to wild-type PSC-derived NK cells, while showing markedly enhanced cytotoxicity against HER2-positive cancer cell lines. These findings demonstrated the potential of the use of PSC-derived anti-HER2 CAR-NK cells as a robust and scalable immunotherapy. In addition, this platform could be extended to produce CAR-NK cells directed against a wide range of tumorassociated antigens. [BMB Reports 2025; 58(11): 475-483]. Chimeric antigen receptor-natural killer (CAR-NK) cells are emerging as a promising platform for allogeneic, cell-based immunotherapy. Among available sources, NK cells derived from pluripotent stem cells (PSCs) provide a renewable and scalable option that overcomes the limitations of primary NK cells. Human epidermal growth factor receptor 2 (HER2), a membrane protein frequently overexpressed in many solid tumors, is an attractive target for cancer immunotherapy. In this study, we designed a green fluorescent protein (GFP)-linked anti-HER2 CAR construct and introduced it into PSCs via lentiviral transduction. Three stable PSC-derived clones (CAR-A, CAR-B, and CAR-C) were established, each co-expressing anti-HER2 CAR with GFP. After differentiation under xeno-free and feeder-free culture conditions, CAR expression was maintained in NK cells. The resulting PSC-derived CAR-NK cells displayed phenotypic and functional features comparable to wild-type PSC-derived NK cells, while showing markedly enhanced cytotoxicity against HER2-positive cancer cell lines. These findings demonstrated the potential of the use of PSC-derived anti-HER2 CAR-NK cells as a robust and scalable immunotherapy. In addition, this platform could be extended to produce CAR-NK cells directed against a wide range of tumor-associated antigens.Chimeric antigen receptor-natural killer (CAR-NK) cells are emerging as a promising platform for allogeneic, cell-based immunotherapy. Among available sources, NK cells derived from pluripotent stem cells (PSCs) provide a renewable and scalable option that overcomes the limitations of primary NK cells. Human epidermal growth factor receptor 2 (HER2), a membrane protein frequently overexpressed in many solid tumors, is an attractive target for cancer immunotherapy. In this study, we designed a green fluorescent protein (GFP)-linked anti-HER2 CAR construct and introduced it into PSCs via lentiviral transduction. Three stable PSC-derived clones (CAR-A, CAR-B, and CAR-C) were established, each co-expressing anti-HER2 CAR with GFP. After differentiation under xeno-free and feeder-free culture conditions, CAR expression was maintained in NK cells. The resulting PSC-derived CAR-NK cells displayed phenotypic and functional features comparable to wild-type PSC-derived NK cells, while showing markedly enhanced cytotoxicity against HER2-positive cancer cell lines. These findings demonstrated the potential of the use of PSC-derived anti-HER2 CAR-NK cells as a robust and scalable immunotherapy. In addition, this platform could be extended to produce CAR-NK cells directed against a wide range of tumor-associated antigens. |
| Author | Jung, Daun Kang, Eunju Jin, Chaeyeon Baek, Young Seok Lee, In Jee Kim, Ji Hyang Hwang, Sae-Byeok Mitalipov, Shoukhrat Han, Jongsuk Kim, Ki Yeon An, Hee Jung Lee, Yeonmi |
| Author_xml | – sequence: 1 givenname: Jongsuk surname: Han fullname: Han, Jongsuk organization: Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea – sequence: 2 givenname: Chaeyeon surname: Jin fullname: Jin, Chaeyeon organization: Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea – sequence: 3 givenname: Sae-Byeok surname: Hwang fullname: Hwang, Sae-Byeok organization: Department of Biomaterials Engineering, School of Medicine, and Biomedical Science, College of Life Science, CHA University, Seongnam 13488; CHA Medical Research Institute, CHA Bundang Medical Center, Seongnam 13488, Korea – sequence: 4 givenname: In Jee surname: Lee fullname: Lee, In Jee organization: Department of Biomaterials Engineering, School of Medicine, and Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea – sequence: 5 givenname: Young Seok surname: Baek fullname: Baek, Young Seok organization: Department of Biomaterials Engineering, School of Medicine, and Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea – sequence: 6 givenname: Daun surname: Jung fullname: Jung, Daun organization: Department of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Korea – sequence: 7 givenname: Ki Yeon surname: Kim fullname: Kim, Ki Yeon organization: Department of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Korea – sequence: 8 givenname: Shoukhrat surname: Mitalipov fullname: Mitalipov, Shoukhrat organization: Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland, OR 97239, USA – sequence: 9 givenname: Ji Hyang surname: Kim fullname: Kim, Ji Hyang organization: Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea – sequence: 10 givenname: Hee Jung surname: An fullname: An, Hee Jung organization: Department of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Korea – sequence: 11 givenname: Yeonmi surname: Lee fullname: Lee, Yeonmi organization: CHA Medical Research Institute, CHA Bundang Medical Center, Seongnam 13488, Korea – sequence: 12 givenname: Eunju surname: Kang fullname: Kang, Eunju organization: Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488; CHA Medical Research Institute, CHA Bundang Medical Center, Seongnam 13488; Department of Biochemistry, School of Medicine, CHA University, Seongnam 13488, Korea |
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| SubjectTerms | Cell Differentiation Cell Line, Tumor Humans Immunotherapy - methods Immunotherapy, Adoptive - methods Killer Cells, Natural - cytology Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Neoplasms - immunology Neoplasms - therapy Pluripotent Stem Cells - cytology Pluripotent Stem Cells - immunology Pluripotent Stem Cells - metabolism Receptor, ErbB-2 - immunology Receptor, ErbB-2 - metabolism Receptors, Chimeric Antigen - immunology Receptors, Chimeric Antigen - metabolism |
| Title | Pluripotent stem cell-derived chimeric antigen receptor-natural killer cells targeting epidermal growth factor receptor 2 for cancer immunotherapy |
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