Generation of chimeric antigen receptor macrophages from human pluripotent stem cells to target glioblastoma

从人类多能干细胞产生嵌合抗原受体巨噬细胞以靶向胶质母细胞瘤

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作者:G Jin, Y Chang, X Bao

Background

Glioblastoma (GBM) is an aggressive brain tumor giving a poor prognosis with the current treatment options. The advent of chimeric antigen receptor (CAR) T-cell therapy revolutionized the field of immunotherapy and has provided a new set of therapeutic options for refractory blood cancers. In an effort to apply this therapeutic approach to solid tumors, various immune cell types and CAR constructs are being studied. Notably, macrophages have recently emerged as potential candidates for targeting solid tumors, attributed to their inherent tumor-infiltrating capacity and abundant presence in the tumor microenvironment. Materials and

Conclusion

Our findings demonstrate the feasibility of generating functional CAR-macrophages from hPSCs for adoptive immunotherapy, thereby opening new avenues for the treatment of solid tumors, particularly GBM.

Methods

In this study, we developed a chemically defined differentiation protocol to generate macrophages from human pluripotent stem cells (hPSCs). A GBM-specific CAR was genetically incorporated into hPSCs to generate CAR hPSC-derived macrophages.

Results

The CAR hPSC-derived macrophages exhibited potent anticancer activity against GBM cells in vitro.

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