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基于抗体的血管肿瘤靶向

Antibody-based vascular tumor targeting.

作者信息

Schliemann Christoph, Neri Dario

机构信息

Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.

出版信息

Recent Results Cancer Res. 2010;180:201-16. doi: 10.1007/978-3-540-78281-0_12.

Abstract

The inhibition of angiogenesis represents a major step toward a more selective and better-tolerated therapy of cancer. An alternative way to take advantage of a tumor's absolute dependence on a functional neovasculature is illustrated by the strategy of "antibody-based vascular tumor targeting." This technology aims at the selective delivery of bioactive molecules to the tumor site by their conjugation to a carrier antibody reactive with a tumor-associated vascular antigen. A number of high-affinity monoclonal antibodies are nowadays available which have demonstrated a remarkable ability to selectively localize to the tumor vasculature. Indeed, some of them have already progressed from preclinical animal experiments to clinical studies in patients with cancer, acting as vehicles for the site-specific pharmacodelivery of proinflammatory cytokines or radionuclides.In this chapter, we present a selection of well-characterized markers of angiogenesis which have proven to be suitable targets for antibody-based vascular targeting approaches. Furthermore, different transcriptomic and proteomic methodologies for the discovery of novel vascular tumor markers are described. In the last two sections, we focus on the discussion of antibody-based vascular tumor targeting strategies for imaging and therapy applications in oncology.

摘要

抑制血管生成是朝着更具选择性和耐受性更好的癌症治疗迈出的重要一步。“基于抗体的血管肿瘤靶向”策略展示了利用肿瘤对功能性新血管系统的绝对依赖性的另一种方法。该技术旨在通过将生物活性分子与与肿瘤相关血管抗原反应的载体抗体偶联,将其选择性递送至肿瘤部位。如今已有多种高亲和力单克隆抗体,它们已证明具有显著的选择性定位于肿瘤血管系统的能力。事实上,其中一些已经从临床前动物实验进展到癌症患者的临床研究,作为促炎细胞因子或放射性核素位点特异性药物递送的载体。在本章中,我们介绍了一系列已被证明适用于基于抗体的血管靶向方法的血管生成特征明确的标志物。此外,还描述了用于发现新型血管肿瘤标志物的不同转录组学和蛋白质组学方法。在最后两节中,我们重点讨论基于抗体的血管肿瘤靶向策略在肿瘤学成像和治疗应用中的情况。

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