Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: crossing the blood-brain barrier divide.
Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: crossing the blood-brain barrier divide.
复制标题
DOI：
10.1517/17425247.2013.808184
复制
发表时间：
2013-07
影响因子：
6.6
通讯作者：
Muzykantov V
中科院分区：
文献类型：
--
作者：
Chacko AM;Li C;Pryma DA;Brem S;Coukos G;Muzykantov V
脑肿瘤本质上很难治疗，这在很大程度上是由于细胞血脑屏障（BBB）限制了治疗剂从体循环递送到肿瘤组织。事实上，没有大分子，包括基于抗体的蛋白质，可以穿透血脑屏障。随着抗体迅速成为高度特异性分子靶向肿瘤抗原的有吸引力的配体，正在研究各种方法以增强这些试剂对颅内肿瘤的接近，用于成像或治疗应用。本文综述了血脑屏障和脑肿瘤血管系统的特点，即血脑肿瘤屏障（BBTB）。针对CNS肿瘤的分子标志物的抗体将被强调，并将讨论目前的策略，以提高这些细胞屏障到脑实质的肿瘤抗体的交付。评估BBB/BBTB渗透性和/或抗体靶向的非侵入性成像方法将作为指导靶向药物向脑肿瘤的最佳递送的手段。临床前和临床研究强调了几种方法在增加脑肿瘤穿过血脑屏障鸿沟方面的潜力。然而，每一种都有其自身的风险和挑战。有巨大的潜力，使用神经影像学策略，以帮助理解和定义的挑战，翻译和优化分子靶向抗体输送到中枢神经系统肿瘤，以改善临床结果。
Brain tumors are inherently difficult to treat in large part due to the cellular blood-brain barriers (BBB) that limit the delivery of therapeutics to the tumor tissue from the systemic circulation. Virtually no large-molecules, including antibody-based proteins, can penetrate the BBB. With antibodies fast becoming attractive ligands for highly specific molecular targeting to tumor antigens, a variety of methods are being investigated to enhance the access of these agents to intracranial tumors for imaging or therapeutic applications. This review describes the characteristics of the BBB and the vasculature in brain tumors, described as the blood-brain tumor barrier (BBTB). Antibodies targeted to molecular markers of CNS tumors will be highlighted, and current strategies for enhancing the delivery of antibodies across these cellular barriers into the brain parenchyma to the tumor will be discussed. Non-invasive imaging approaches to assess BBB/BBTB permeability and/or antibody targeting will be presented as a means of guiding the optimal delivery of targeted agents to brain tumors. Pre-clinical and clinical studies highlight the potential of several approaches in increasing brain tumor delivery across the blood-brain barrier divide. However, each carries its own risks and challenges. There is tremendous potential in using neuroimaging strategies to assist in understanding and defining the challenges to translating and optimizing molecularly-targeted antibody delivery to CNS tumors to improve clinical outcomes.
登录
查看更多内容
影响因子：
2.9
作者：
Brown, RC;Egleton, RD;Davis, TP
通讯作者：
Davis, TP
影响因子：
9.9
作者：
CHAMBERLAIN, MC;MUROVIC, JA;LEVIN, VA
通讯作者：
LEVIN, VA
影响因子：
6.2
作者：
Agarwal S;Sane R;Oberoi R;Ohlfest JR;Elmquist WF
通讯作者：
Elmquist WF
影响因子：
--
作者：
Baumann, Brian C.;Kao, Gary D.;Dorsey, Jay F.
通讯作者：
Dorsey, Jay F.
影响因子：
5.5
作者：
BUTT, AM;JONES, HC;ABBOTT, NJ
通讯作者：
ABBOTT, NJ