Generation of anti-GD2 CAR macrophages from human pluripotent stem cells for cancer immunotherapies.
Stem Cell Reports
; 18(2): 585-596, 2023 02 14.
Article
em En
| MEDLINE
| ID: mdl-36638788
ABSTRACT
Macrophages armed with chimeric antigen receptors (CARs) provide a potent new option for treating solid tumors. However, genetic engineering and scalable production of somatic macrophages remains significant challenges. Here, we used CRISPR-Cas9 gene editing methods to integrate an anti-GD2 CAR into the AAVS1 locus of human pluripotent stem cells (hPSCs). We then established a serum- and feeder-free differentiation protocol for generating CAR macrophages (CAR-Ms) through arterial endothelial-to-hematopoietic transition (EHT). CAR-M produced by this method displayed a potent cytotoxic activity against GD2-expressing neuroblastoma and melanoma in vitro and neuroblastoma in vivo. This study provides a new platform for the efficient generation of off-the-shelf CAR-Ms for antitumor immunotherapy.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Pluripotentes
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Receptores de Antígenos Quiméricos
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Melanoma
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Neuroblastoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article