CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Leveraging CAR macrophages targeting c-Met for precision immunotherapy in pancreatic cancer: insights from single-cell multi-omics.
Leveraging CAR macrophages targeting c-Met for precision immunotherapy in pancreatic cancer: insights from single-cell multi-omics.
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靶向 c-Met 的 CAR 巨噬细胞代表了一种有前景的胰腺癌治疗策略，能够靶向清除 CSCs 并破坏肿瘤血管生成。本研究凸显了单细胞多组学在指导精准免疫疗法开发方面的潜力。
胰腺癌因其预后差和对传统疗法的耐药性而闻名，这在很大程度上是由于癌症干细胞（CSCs）的存在和侵袭性血管生成。有效靶向这些CSCs及其相关的血管生成通路对于有效治疗至关重要。本研究利用单细胞多组学探索了一种新的治疗方法，即工程化嵌合抗原受体（CAR）巨噬细胞靶向胰腺CSCs上的c-Met蛋白。
我们采用单细胞RNA测序分析胰腺癌组织，确定c-Met为CSCs的关键标志物。利用慢病毒系统工程化改造CAR巨噬细胞以表达c-Met特异性受体。在体外评估了这些CAR巨噬细胞对胰腺CSCs的吞噬效率及其抑制血管生成的能力。在胰腺癌小鼠模型中评估了CAR巨噬细胞的体内疗效。
CAR 巨噬细胞对 c-Met + CSCs 表现出高特异性，显著增强吞噬作用并减少 VEGFA、FGF2 和 ANGPT 等血管生成因子的分泌。在体内，这些巨噬细胞显著抑制肿瘤生长和血管生成，延长了胰腺癌荷瘤小鼠的生存期。
Pancreatic cancer is known for its poor prognosis and resistance to conventional therapies, largely due to the presence of cancer stem cells (CSCs) and aggressive angiogenesis. Effectively targeting these CSCs and associated angiogenic pathways is crucial for effective treatment. This study leverages single-cell multi-omics to explore a novel therapeutic approach involving Chimeric Antigen Receptor (CAR) macrophages engineered to target the c-Met protein on pancreatic CSCs.
We employed single-cell RNA sequencing to analyze pancreatic cancer tissue, identifying c-Met as a key marker of CSCs. CAR macrophages were engineered using a lentiviral system to express a c-Met-specific receptor. The phagocytic efficiency of these CAR macrophages against pancreatic CSCs was assessed in vitro, along with their ability to inhibit angiogenesis. The in vivo efficacy of CAR macrophages was evaluated in a mouse model of pancreatic cancer.
CAR macrophages demonstrated high specificity for c-Met + CSCs, significantly enhancing phagocytosis and reducing the secretion of angiogenic factors such as VEGFA, FGF2, and ANGPT. In vivo, these macrophages significantly suppressed tumor growth and angiogenesis, prolonging survival in pancreatic cancer-bearing mice.
CAR macrophages targeting c-Met represent a promising therapeutic strategy for pancreatic cancer, offering targeted elimination of CSCs and disruption of tumor angiogenesis. This study highlights the potential of single-cell multi-omics in guiding the development of precision immunotherapies.
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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