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针对神经胶质瘤干细胞的免疫疗法——见解与展望。

Immunotherapy targeting glioma stem cells--insights and perspectives.

机构信息

Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8361 West Third Street, Suite 800 E, Los Angeles, CA 90048, USA.

出版信息

Expert Opin Biol Ther. 2012 Feb;12(2):165-78. doi: 10.1517/14712598.2012.648180. Epub 2011 Dec 26.

Abstract

INTRODUCTION

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary malignant brain tumor. Although progress has been made in current conventional therapies for GBM patients, the effect of these advances on clinical outcomes has been disappointing. Recent research into the origin of cancers suggest that GBM cancer stem cells (GSC) are the source of initial tumor formation, resistance to current conventional therapeutics and eventual patient relapse. Currently, there are very few studies that apply immunotherapy to target GSC.

AREAS COVERED

CD133, a cell surface protein, is used extensively as a surface marker to identify and isolate GSC in malignant glioma. We discuss biomarkers such as CD133, L1-cell adhesion molecule (L1-CAM), and A20 of GSC. We review developing novel treatment modalities, including immunotherapy strategies, to target GSC.

EXPERT OPINION

There are very few reports of preclinical studies targeting GSC. Identification and validation of unique molecular signatures and elucidation of signaling pathways involved in survival, proliferation and differentiation of GSC will significantly advance this field and provide a framework for the rational design of a new generation of antigen-specific, anti-GSC immunotherapy- and nanotechnology-based targeted therapyies. Combined with other therapeutic avenues, GSC-targeting therapies may represent a new paradigm to treat GBM patients.

摘要

简介

多形性胶质母细胞瘤(GBM)是最具侵袭性和致命性的原发性恶性脑肿瘤。尽管目前针对 GBM 患者的常规治疗已经取得了进展,但这些进展对临床结果的影响仍令人失望。最近对癌症起源的研究表明,GBM 癌症干细胞(GSC)是肿瘤初始形成、对现有常规疗法的耐药性以及最终患者复发的根源。目前,很少有研究将免疫疗法应用于针对 GSC。

涵盖领域

CD133 是一种细胞表面蛋白,被广泛用作表面标记物,用于鉴定和分离恶性神经胶质瘤中的 GSC。我们讨论了 GSC 的标志物,如 CD133、L1-细胞黏附分子(L1-CAM)和 A20。我们回顾了开发新的治疗方式,包括免疫疗法策略,以针对 GSC。

专家意见

针对 GSC 的临床前研究报告很少。鉴定和验证独特的分子特征,并阐明涉及 GSC 存活、增殖和分化的信号通路,将极大地推动这一领域的发展,并为新一代针对 GSC 的抗原特异性免疫疗法和基于纳米技术的靶向治疗的合理设计提供框架。结合其他治疗途径,针对 GSC 的治疗方法可能代表治疗 GBM 患者的新范例。

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