Biological impediments to monoclonal antibody-based cancer immunotherapy.
Biological impediments to monoclonal antibody-based cancer immunotherapy.
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DOI：
10.1158/1535-7163.1493.3.11
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发表时间：
2004-11
影响因子：
5.7
通讯作者：
J. Christiansen;A. Rajasekaran
中科院分区：
文献类型：
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作者：
J. Christiansen;A. Rajasekaran
抗体利用正常组织和恶性组织之间的抗原差异并产生多种抗肿瘤反应的能力为常规形式的治疗提供了显著的优势。几种单克隆抗体（mAb）已经被证明是相对良好的耐受性和有效的治疗许多不同的恶性疾病。然而，单克隆抗体必须克服实质性的障碍，以达到靶细胞上呈递的具有治疗价值的抗原。免疫内施用的抗体必须避免宿主免疫应答，并与肿瘤细胞上抗原的低表达或异质表达相抗衡。抗体还必须克服通往实体瘤块的重要物理屏障，包括血管内皮、基质屏障、高间质压和上皮屏障。在这里，我们回顾了单克隆抗体作为有效治疗形式的应用和发展，特别关注成功治疗的障碍和障碍，并讨论了克服这些障碍和提高单克隆抗体治疗疗效的策略。
The ability of antibodies to exploit antigenic differences between normal and malignant tissues and to exact a variety of antitumor responses offers significant advantages to conventional forms of therapy. Several monoclonal antibodies (mAb) have already proved to be relatively well tolerated and effective for the treatment of many different malignant diseases. However, mAbs must overcome substantial obstacles to reach antigens presented on target cells to be of therapeutic value. Intravenously administered antibodies must avoid host immune response and contend with low or heterogeneous expression of antigen on tumor cells. Antibodies must also overcome significant physical barriers en route to a solid tumor mass, including the vascular endothelium, stromal barriers, high interstitial pressure, and epithelial barriers. Here we review the application and evolution of mAbs as effective forms of treatment, with particular attention to the barriers and impediments to successful treatment and discuss strategies to overcome these barriers and improve the efficacy of mAb-based therapy.