ErbB-directed immunotherapy:: Antibodies in current practice and promising new agents
ErbB-directed immunotherapy:: Antibodies in current practice and promising new agents
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DOI：
10.1016/j.imlet.2007.12.001
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发表时间：
2008-03-01
影响因子：
4.4
通讯作者：
Vereb, Gyoergy
中科院分区：
文献类型：
--
作者：
Friedlander, Elza;Barok, Mark;Vereb, Gyoergy
ErbB 家族因其在肿瘤发生中的重要性而闻名。作为不良预后标志物，过度表达或突变的 ErbB1 和 ErbB2 在各种癌症的分子诊断中具有重要作用，但作为膜蛋白，通常选择性地在肿瘤组织中表达，它们可以成为激酶抑制剂或治疗性抗体的靶标。除了曲妥珠单抗（第一个被 FDA 批准用于治疗实体瘤的人源化抗体）之外，现在许多人源化抗体正处于后期临床试验中，或已经获得批准。抗体与放射性同位素、细胞毒剂或装载化疗药物的脂质体的缀合导致比其亲本“非武装”抗体提高了治疗效率。具有更好药效特性的新型工程化抗体衍生物也已上市，可以针对更广泛的患者群体中的 ErbB1 或 ErbB2 阳性癌症。在这篇综述中，我们讨论了 ErbB 靶向的生物学和临床背景，并描述了针对 ErbB I（西妥昔单抗、帕尼单抗、马妥珠单抗、尼妥珠单抗、ICR62、mAb 528、ch806 和 MDX-447）和 ErbB2（曲妥珠单抗、帕妥珠单抗、MDX-H210,2B1、 正在进行临床试验或已获批准的 C6.5xscFv(NM3E2)、ertumaxomab 和 FRP-5 衍生物，以及各种相关的缀合和工程策略。还讨论了与曲妥珠单抗治疗临床耐药性这一普遍问题相关的最新数据。 (C) 2007 Elsevier B.V. 保留所有权利。
The ErbB family is well known for its significance in oncogenesis. As bad prognostic markers, overexpressed or mutated ErbB1 and ErbB2 have an important role in the molecular diagnosis of various cancers, but as membrane proteins, expressed often selectively in tumor tissues, they can be targeted with kinase inhibitors or therapeutic antibodies. In addition to trastuzumab, the first humanized antibody that was approved for the therapy of solid tumors by the FDA, now many humanized antibodies are in late clinical trials, or already approved. Conjugation of antibodies with radioactive isotopes, cytotoxic agents or liposomes loaded with chemotherapeutic drugs led to improved therapeutic efficiency over their parent "unarmed" antibodies. Novel, engineered antibody derivates with better pharmacodynamic properties are also available and allow the targeting of ErbB1 or ErbB2 positive cancers in a wider patient population. In this review, we discuss the biological and clinical background of ErbB targeting, and describe the most successful antibodies against ErbB I (cetuximab, panitumumab, matuzumab, nimotuzumab, ICR62, mAb 528, ch806 and MDX-447) and ErbB2 (trastuzumab, pertuzumab, MDX-H210,2B1, C6.5xscFv(NM3E2), ertumaxomab and FRP-5 derivates) that are in clinical trials or already approved, along with the various relevant conjugation and engineering strategies. Recent data pertinent to the prevalent problem of clinical resistance to treatment with trastuzumab are also discussed. (C) 2007 Elsevier B.V. All rights reserved.