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Updated: Jan 11, 2026
Generation of Human Microglia to Combine Them with Retinal Organoids for Improved Disease Modeling
Published on: July 26, 2024
GD2-CAR-Engineered Microglia Exhibit Antitumor Effects in Organoids and Animal Models of Retinoblastoma
Jia Xu1, Yimeng Gao1, Jinyi Wang1
1Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
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.
Insights
Researchers engineered microglia cells to express chimeric antigen receptors (CARs) to target retinoblastoma (RB). These CAR-microglia demonstrated significant antitumor effects in preclinical models, showing promise for treating this childhood eye cancer.
Area of Science:
- Ophthalmology
- Immunology
- Cancer Biology
Background:
- Retinoblastoma (RB) is the most common childhood intraocular malignancy.
- Chimeric antigen receptor (CAR) T-cell therapy shows promise for cancer treatment.
- The potential of microglia, resident retinal immune cells, for CAR therapy in RB is unexplored.
Purpose of the Study:
- To engineer human microglia to express CARs targeting retinoblastoma.
- To evaluate the in vitro and in vivo antitumor efficacy of CAR-microglia against RB.
Main Methods:
- Generated human GD2 CAR-microglia from induced pluripotent stem cells.
- Verified CAR expression using fluorescence microscopy, PCR, and flow cytometry.
- Assessed antitumor effects in RB cell lines, organoids, and xenograft models using various imaging and molecular techniques.
Main Results:
- Developed GD2 CAR-microglia with significant phagocytic activity against RB cells and organoids.
- CAR-microglia treatment led to reduced tumor growth and prolonged survival in mice with RB xenografts.
- Confirmed CAR presence and function through immunofluorescence, flow cytometry, and RNA sequencing.
Conclusions:
- GD2 CAR-engineered microglia exhibit potent antitumor effects against retinoblastoma.
- CAR-microglia represent a promising therapeutic strategy for retinoblastoma.
- Further development of CAR-microglia therapy for RB is warranted.
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