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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Veröffentlicht in:BMB reports Jg. 58; H. 11; S. 475
Hauptverfasser: Han, Jongsuk, Jin, Chaeyeon, Hwang, Sae-Byeok, Lee, In Jee, Baek, Young Seok, Jung, Daun, Kim, Ki Yeon, Mitalipov, Shoukhrat, Kim, Ji Hyang, An, Hee Jung, Lee, Yeonmi, Kang, Eunju
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Korea (South) 01.11.2025
Schlagworte:
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
ISSN:1976-670X, 1976-670X
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Zusammenfassung: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].
Bibliographie:content type line 23
SourceType-Scholarly Journals-1
ObjectType-News-1
ISSN:1976-670X
1976-670X
DOI:10.5483/bmbrep.2025-0137