ArticleInvestigative ophthalmology & visual science2025
GD2-CAR-Engineered Microglia Exhibit Antitumor Effects in Organoids and Animal Models of Retinoblastoma.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Purpose: Retinoblastoma (RB) is the most prevalent intraocular malignancy in children, which significantly impacts patients' quality of life. Chimeric antigen receptor (CAR) immune cell therapies opened a door to treating tumors. However, whether microglia, the resident immune cell in the retina, could be engineered to treat retinoblastoma remains unknown. The purpose of this study is to generate human CAR-microglia and to investigate the antitumor effects of CAR-microglia in RB. Methods: The presence of CAR in microglia cells was verified using a fluorescence microscope, PCR, and flow cytometry analysis. The CAR-microglia generated from induced pluripotent stem cells were identified by immunofluorescence, flow cytometry analysis, and RNA sequencing (RNA-seq). The antitumor effects of CAR-microglia in retinoblastoma are investigated in vitro and in vivo by live imaging, flow cytometry analysis, RNA-seq, quantitative real-time PCR, cell viability analysis, cell bioluminescence analysis, ELISA, optical coherence tomography, fundus photography, bioluminescence imaging, and hematoxylin and eosin staining. Results: We developed human GD2 CAR-microglia and found that they exhibited a remarkable phagocytic effect against retinoblastoma Y79 cells and retinoblastoma organoids, as demonstrated by live imaging. Moreover, GD2 CAR-microglia administration to immunodeficient mice carrying a retinoblastoma xenograft resulted in a significant reduction in tumor growth and prolonged survival. Conclusions: Our findings demonstrate a potent antitumor effect of GD2-CAR-engineered microglia in retinoblastoma, offering compelling evidence to support the continued development of CAR-microglia as a therapeutic strategy for this disease.
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