Generation of anti-GD2 CAR macrophages from human pluripotent stem cells for cancer immunotherapies

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...

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Detalles Bibliográficos
Autores principales: Zhang, Jue, Webster, Sarah, Duffin, Bret, Bernstein, Matthew N., Steill, John, Swanson, Scott, Forsberg, Matthew H., Bolin, Jennifer, Brown, Matthew E., Majumder, Aditi, Capitini, Christian M., Stewart, Ron, Thomson, James A., Slukvin, Igor I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968983/
https://www.ncbi.nlm.nih.gov/pubmed/36638788
http://dx.doi.org/10.1016/j.stemcr.2022.12.012
Descripción
Sumario: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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