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通过原位激活树突状细胞,使用EphrinA1-PE38/GM-CSF壳聚糖纳米颗粒治疗荷兰大鼠胶质瘤模型。

Treatment of Dutch rat models of glioma using EphrinA1-PE38/GM-CSF chitosan nanoparticles by in situ activation of dendritic cells.

作者信息

Li Ming, Wang Bin, Wu Zhonghua, Shi Xiwen, Zhang Jiadong, Han Shuangyin

机构信息

Department of Neurosurgery, the People's Hosptial of Zhengzhou University, 7 Weiwu Road, Zhengzhou City, Henan Province, 450003, People's Republic of China.

Central Research Lab, the People's Hosptial of Zhengzhou University, 7 Weiwu Road, Zhengzhou City, Henan Province, 450003, People's Republic of China.

出版信息

Tumour Biol. 2015 Sep;36(10):7961-6. doi: 10.1007/s13277-015-3486-z. Epub 2015 May 10.

Abstract

Although dendritic cells (DCs) used in DC-based immunotherapy are loaded with tumor-associated antigens, the antitumor immune response is effectively stimulated in cytotoxic specific T lymphocytes (CTLs), thereby achieving targeted killing of tumor cells without harming surrounding normal cells. This makes it a highly promising new form of therapy. In this study, we successfully created chitosan-coated EphrinA1-PE38/GM-CSF nanoparticles and transplanted them into tumor-bearing rats, resulting in the effective killing of glioma tissue and a prolonged life span. Further immunohistochemistry and flow cytometry studies revealed that the treatment was effective in increasing the number of dendritic cell activations under an immunomodulatory response. These results suggest that chitosan-coated EphrinA1-PE38/GM-CSF nanoparticles may be effective in inducing in situ activation of DCs in glioma-bearing rats, thereby generating DC vaccines in vivo.

摘要

尽管用于基于树突状细胞(DC)的免疫疗法中的树突状细胞负载了肿瘤相关抗原,但细胞毒性特异性T淋巴细胞(CTL)中抗肿瘤免疫反应被有效刺激,从而实现对肿瘤细胞的靶向杀伤而不损害周围正常细胞。这使其成为一种极具前景的新型治疗方式。在本研究中,我们成功制备了壳聚糖包被的EphrinA1-PE38/GM-CSF纳米颗粒,并将其移植到荷瘤大鼠体内,有效杀伤了胶质瘤组织并延长了生存期。进一步的免疫组织化学和流式细胞术研究表明,该治疗在免疫调节反应下有效增加了树突状细胞激活的数量。这些结果表明,壳聚糖包被的EphrinA1-PE38/GM-CSF纳米颗粒可能有效诱导荷胶质瘤大鼠体内DC的原位激活,从而在体内产生DC疫苗。

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