Friedländer Elza, Barok Márk, Szöllosi János, Vereb György
Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Immunol Lett. 2008 Mar 15;116(2):126-40. doi: 10.1016/j.imlet.2007.12.001. Epub 2007 Dec 26.
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 ErbB1 (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.
表皮生长因子受体（ErbB）家族在肿瘤发生过程中的重要作用广为人知。作为不良预后标志物，过表达或突变的ErbB1和ErbB2在多种癌症的分子诊断中具有重要作用，但作为膜蛋白，它们通常在肿瘤组织中选择性表达，因此可以用激酶抑制剂或治疗性抗体进行靶向治疗。除了曲妥珠单抗（第一种被美国食品药品监督管理局（FDA）批准用于实体瘤治疗的人源化抗体）外，现在许多人源化抗体正处于临床试验后期，或已获批准。将抗体与放射性同位素、细胞毒性剂或装载化疗药物的脂质体结合，相较于其亲本“未武装”抗体，可提高治疗效果。还出现了具有更好药效学特性的新型工程化抗体衍生物，能够在更广泛的患者群体中靶向ErbB1或ErbB2阳性癌症。在本综述中，我们讨论了ErbB靶向治疗的生物学和临床背景，并描述了针对ErbB1（西妥昔单抗、帕尼单抗、美妥昔单抗、尼妥珠单抗、ICR62、单克隆抗体528、ch806和MDX - 447）和ErbB2（曲妥珠单抗、帕妥珠单抗、MDX - H210、2B1、C6.5xscFv(NM3E2)、厄妥昔单抗和FRP - 5衍生物）的最成功的抗体，这些抗体正处于临床试验阶段或已获批准，同时还介绍了各种相关的结合和工程策略。此外，还讨论了与曲妥珠单抗临床耐药这一普遍问题相关的最新数据。
