CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
从人多能干细胞生成靶向胶质母细胞瘤的嵌合抗原受体巨噬细胞
英文原题：Generation of chimeric antigen receptor macrophages from human pluripotent stem cells to target glioblastoma.
查看英文原题
Generation of chimeric antigen receptor macrophages from human pluripotent stem cells to target glioblastoma.
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研究概要
我们的研究结果证明了从 hPSCs 生成功能性 CAR-巨噬细胞用于过继性免疫治疗的可行性，从而为实体瘤，尤其是 GBM 的治疗开辟了新途径。
研究思路结论见上方概要
背景
胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，在当前治疗方案下预后较差。嵌合抗原受体（CAR）T细胞疗法的出现彻底改变了免疫治疗领域，并为难治性血液癌症提供了一系列新的治疗选择。为了将这种治疗方法应用于实体瘤，多种免疫细胞类型和CAR构建体正在研究中。值得注意的是，巨噬细胞因其固有的肿瘤浸润能力和在肿瘤微环境中的大量存在，最近已成为靶向实体瘤的潜在候选者。
方法
在本研究中，我们开发了一种化学成分明确的分化方案，用于从人类多能干细胞（hPSCs）生成巨噬细胞。将GBM特异性CAR基因整合到hPSCs中，以生成CAR hPSC来源的巨噬细胞。
结果
CAR hPSC 来源的巨噬细胞在体外对 GBM 细胞表现出强效抗癌活性。
展开英文摘要原文
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 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 .
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.
论文信息
- 作者
- Jin G、Chang Y、Bao X
- 单位
- Davidson School of Chemical Engineering, Purdue University, West Lafayette.
- 期刊
- Immuno-oncology technology2023 Dec
- 原文标识
- PubMed 38192614 · DOI 10.1016/j.iotech.2023.100409
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