Generation of chimeric antigen receptor macrophages from human pluripotent stem cells to target glioblastoma.
Generation of chimeric antigen receptor macrophages from human pluripotent stem cells to target glioblastoma.
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DOI：
10.1016/j.iotech.2023.100409
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发表时间：
2023-12
期刊：
影响因子：
--
通讯作者：
Bao, X
中科院分区：
文献类型：
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作者：
Jin, G;Chang, Y;Bao, X
胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，目前的治疗方案预后不良。嵌合抗原受体（CAR）T细胞疗法的出现彻底改变了免疫疗法领域，并为难治性血癌提供了一套新的治疗选择。为了将这种治疗方法应用于实体瘤，正在研究各种免疫细胞类型和CAR构建体。值得注意的是，巨噬细胞最近已经成为靶向实体瘤的潜在候选者，这归因于它们固有的肿瘤浸润能力和在肿瘤微环境中的丰富存在。在这项研究中，我们开发了一种化学定义的分化方案，从人多能干细胞（hPSC）产生巨噬细胞。将GBM特异性CAR遗传并入hPSC中以产生CAR hPSC衍生的巨噬细胞。CAR hPSC衍生的巨噬细胞在体外表现出针对GBM细胞的有效抗癌活性。我们的研究结果证明了从hPSC产生功能性CAR-巨噬细胞用于过继免疫治疗的可行性，从而为实体瘤，特别是GBM的治疗开辟了新的途径。巨噬细胞是实体瘤免疫治疗的潜在靶点。化学定义的方案从人多能干细胞（hPSC）产生巨噬细胞。来自hPSC的工程化GBM特异性CAR-巨噬细胞表现出增强的抗癌细胞活性。该研究强调了采用来自hPSC的CAR-巨噬细胞进行免疫治疗的可行性。
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. 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. The CAR hPSC-derived macrophages exhibited potent anticancer activity against GBM cells in vitro. 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. Macrophages are potential candidates for targeting solid tumor in immunotherapy. A chemically defined protocol generates macrophages from human pluripotent stem cells (hPSCs). The engineered GBM-specific CAR-macrophages from hPSCs exhibited enhanced anti-cancer cell activity. The study highlights the feasibility of adopting CAR-macrophages from hPSCs for immunotherapy.