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
推进肿瘤靶向化疗-免疫治疗：CAR-M 衍生外泌体-药物偶联物的开发
英文原题：Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate.
查看英文原题
Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate.
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中文摘要
传统抗体-药物偶联物（ADC）主要通过细胞毒性载荷的化疗或免疫调节剂的免疫治疗来抑制肿瘤生长。然而，单一治疗模式可能限制其探索。在此，我们利用来自CAR-M细胞的CAR-外泌体作为靶向药物载体，开发了一种新型药物偶联物，称为CAR-EDC（CAR-M来源外泌体-药物偶联物），该载体含有高水平CXCL10。CAR-外泌体可显著增强T淋巴细胞的免疫激活和迁移能力，并促进其分化为CD8+ T细胞。它还增加了M1巨噬细胞的比例。共价装载SN-38的CAR-EDC通过CAR分子介导的内吞作用被内化进入Raji细胞。它在体内表现出优异的抗肿瘤活性，既得益于SN38的化疗，也得益于CXCL10介导的抗肿瘤免疫治疗。总体而言，本研究提供了一种外泌体-药物偶联系统，通过化疗和免疫治疗的协同作用，其抗肿瘤效果优于传统ADC。
展开英文摘要原文
Traditional antibody-drug conjugates (ADCs) mainly suppress tumor growth through either chemotherapy with cytotoxic payloads or immunotherapy with immuno-modulators.
However, a single therapeutic modality may limit their exploration.
Herein, we developed a new type of drug conjugate termed CAR-EDC (CAR-M-derived exosome-drug conjugate) by using CAR-exosomes from CAR-M cells as the targeting drug carrier that contains a high level of CXCL10. CAR-exosomes could significantly enhance the immunological activation and migratory capacity of T lymphocytes and promote their differentiation into CD8+ T cells. It also increased the proportion of M1 macrophages.
The CAR-EDC, covalently loaded with SN-38, was internalized into Raji cells through endocytosis mediated by the CAR molecules. It exerted excellent antitumor activity in vivo by virtue of not only chemotherapy by SN38 but also immunotherapy by CXCL10-mediated antitumor immunity. Generally, this study provides an exosome-drug conjugate system with enhanced antitumor effects over traditional ADCs through the synergism of chemotherapy and immunotherapy.
论文信息
- 作者
- Jiang Y、Xu X、Fan D、Liu P、Zhou M、Cheng M、Huang J、Luo Y
- 单位
- Laboratory of Human Diseases and Immunotherapy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Journal of medicinal chemistry2024 Aug 22
- 原文标识
- PubMed 39041307 · DOI 10.1021/acs.jmedchem.4c00753