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基于抗体的药物及其通过血脑屏障进行递送以用于神经胶质瘤靶向治疗和免疫治疗的进展。

Advances in antibody-based drugs and their delivery through the blood-brain barrier for targeted therapy and immunotherapy of gliomas.

作者信息

Huang Xin, Shi Shuyou, Wang Hongrui, Zhao Tiesuo, Wang Yibo, Huang Sihua, Su Yingying, Zhao Chunyan, Yang Ming

机构信息

College of Basic Medical Sciences, Jilin University, Changchun 130021, Jilin Province, China.

Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.

出版信息

Int Immunopharmacol. 2023 Apr;117:109990. doi: 10.1016/j.intimp.2023.109990. Epub 2023 Mar 10.

Abstract

Gliomas are highly invasive and are the most common type of primary malignant brain tumor. The routine treatments for glioma include surgical resection, radiotherapy, and chemotherapy. However, glioma recurrence and patient survival remain unsatisfactory after employing these traditional treatment approaches. With the rapid development of molecular immunology, significant breakthroughs have been made in targeted glioma therapy and immunotherapy. Antibody-based therapy has excellent advantages in treating gliomas due to its high specificity and sensitivity. This article reviewed various targeted antibody drugs for gliomas, including anti-glioma surface marker antibodies, anti-angiogenesis antibodies, and anti-immunosuppressive signal antibodies. Notably, many antibodies have been validated clinically, such as bevacizumab, cetuximab, panitumumab, and anti-PD-1 antibodies. These antibodies can improve the targeting of glioma therapy, enhance anti-tumor immunity, reduce the proliferation and invasion of glioma, and thus prolong the survival time of patients. However, the existence of the blood-brain barrier (BBB) has caused significant difficulties in drug delivery for gliomas. Therefore, this paper also summarized drug delivery methods through the BBB, including receptor-mediated transportation, nano-based carriers, and some physical and chemical methods for drug delivery. With these exciting advancements, more antibody-based therapies will likely enter clinical practice and allow more successful control of malignant gliomas.

摘要

神经胶质瘤具有高度侵袭性,是最常见的原发性恶性脑肿瘤类型。神经胶质瘤的常规治疗方法包括手术切除、放疗和化疗。然而,采用这些传统治疗方法后,神经胶质瘤的复发情况和患者生存率仍不尽人意。随着分子免疫学的快速发展,神经胶质瘤的靶向治疗和免疫治疗取得了重大突破。基于抗体的疗法因其高特异性和敏感性,在治疗神经胶质瘤方面具有出色的优势。本文综述了多种针对神经胶质瘤的靶向抗体药物,包括抗神经胶质瘤表面标志物抗体、抗血管生成抗体和抗免疫抑制信号抗体。值得注意的是,许多抗体已在临床上得到验证,如贝伐单抗、西妥昔单抗、帕尼单抗和抗程序性死亡蛋白1(PD-1)抗体。这些抗体可以提高神经胶质瘤治疗的靶向性,增强抗肿瘤免疫力,减少神经胶质瘤的增殖和侵袭,从而延长患者的生存时间。然而,血脑屏障(BBB)的存在给神经胶质瘤的药物递送带来了重大困难。因此,本文还总结了通过血脑屏障的药物递送方法,包括受体介导的转运、纳米载体以及一些物理和化学药物递送方法。随着这些令人振奋的进展,更多基于抗体的疗法可能会进入临床实践,并更成功地控制恶性神经胶质瘤。

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