CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
引导 CAR-T 细胞靶向肿瘤血管以治疗实体瘤
英文原题：Directing CAR T cells towards the tumor vasculature for the treatment of solid tumors.
查看英文原题
Directing CAR T cells towards the tumor vasculature for the treatment of solid tumors.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法在实体瘤中的成功应用仍需克服重大障碍。CAR-T 细胞必须穿越血管屏障，而肿瘤血管的无反应状态阻碍了这一过程，其特征是内皮细胞上白细胞黏附分子表达水平受到抑制。实体瘤微环境中的其他免疫抑制机制可影响CAR-T 细胞的浸润、活性和持久性。将CAR-T 细胞重定向至肿瘤血管可能是一种解决方案，因为肿瘤内皮细胞的分子靶标可直接从血液中被识别。在本综述中，我们讨论了CAR-T 细胞疗法针对实体瘤的最新进展，重点关注靶向肿瘤血管。此外，我们探讨了通过工程化改造CAR-T 细胞以增强其运输、安全性和有效性来克服挑战和障碍的机会。
展开英文摘要原文
For successful application of chimeric antigen receptor (CAR) T cell therapy in solid tumors, major hurdles have to be overcome. CAR T cells have to cross the vascular barrier, which is hampered by the anergic state of the tumor vasculature, characterized by suppressed levels of leukocyte adhesion molecules on the endothelium.
Additional immunosuppressive mechanisms in the solid tumor microenvironment can affect infiltration, activity and persistence of CAR T cells. Redirecting CAR T cells towards the tumor vasculature poses a possible solution, as molecular targets of tumor endothelial cells can be directly engaged from within the blood. In this review, we discuss recent advances in CAR T cell therapy against solid tumors, with a focus on targeting the tumor vasculature.
Furthermore, we discuss opportunities to overcome challenges and barriers through engineering of CAR T cells to enhance trafficking, safety and efficacy.
论文信息
- 作者
- Akbari P、Katsarou A、Daghighian R、van Mil LWHG、Huijbers EJM、Griffioen AW、van Beijnum JR
- 第一作者单位
- Amsterdam UMC, Vrije Universiteit Amsterdam, Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, the Netherlands.Netherlands
- 通讯作者单位
- Amsterdam UMC, Vrije Universiteit Amsterdam, Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, the Netherlands. Electronic address: j.vanbeijnum01@gmail.com.Netherlands
- 文献类型
- 综述 · 非美国政府资助研究
- 期刊
- Biochimica et biophysica acta. Reviews on cancer2022 May
- 原文标识
- PubMed 35202772 · DOI 10.1016/j.bbcan.2022.188701