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基于 uPAR 结合片段设计嵌合抗原受体可触发针对表达 uPAR 的卵巢癌细胞的抗肿瘤疗效。

Basing on uPAR-binding fragment to design chimeric antigen receptors triggers antitumor efficacy against uPAR expressing ovarian cancer cells.

机构信息

Department of Gynecology and Obstetrics, the Second Hospital of Jilin University, Changchun, 130041, Jilin, China.

出版信息

Biomed Pharmacother. 2019 Sep;117:109173. doi: 10.1016/j.biopha.2019.109173. Epub 2019 Jul 1.

Abstract

Due to the success of chimeric antigen receptors (CARs) in hematological tumors, CARs are also being studied to treat solid tumors. Improving the ability of CARs to penetrate solid tumor tissues is one of the biggest challenges. As the most malignant cancer of the female reproductive system, the survival rate of ovarian cancer has not been significantly improved by traditional therapy methods; therefore, it is necessary to develop new therapeutic targets and new immunotherapy methods for ovarian cancer. UPAR is a glysocylphosphatidylinositol (GPI) anchoring membrane protein that is differentially expressed in normal tissues and ovarian cancer tissues. It has been shown that uPAR up-regulation promotes tumor development, proliferation, invasion, and metastasis, and uPAR is also up-regulated in tumor matrix components. In our study, CARs were designed using the natural ligand binding fragment of uPAR for ovarian cancer.

摘要

由于嵌合抗原受体 (CARs) 在血液肿瘤中的成功,CARs 也正在被研究用于治疗实体瘤。提高 CARs 穿透实体瘤组织的能力是最大的挑战之一。作为女性生殖系统最恶性的癌症,卵巢癌的存活率并没有通过传统的治疗方法得到显著提高;因此,有必要为卵巢癌开发新的治疗靶点和新的免疫治疗方法。UPAR 是一种糖基磷脂酰肌醇 (GPI) 锚定膜蛋白,在正常组织和卵巢癌组织中差异表达。已经表明 uPAR 的上调促进了肿瘤的发展、增殖、侵袭和转移,并且肿瘤基质成分中也上调了 uPAR。在我们的研究中,使用 uPAR 的天然配体结合片段设计了用于卵巢癌的 CARs。

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