Department of Animal and Veterinary Science, University of Idaho, Moscow, ID, USA.
MAbs. 2011 Sep-Oct;3(5):467-78. doi: 10.4161/mabs.3.5.16089. Epub 2011 Sep 1.
Due to their excellent specificity for a single epitope, monoclonal antibodies (mAbs) present a means of influencing the function of cells at the molecular level. In particular they show great promise in the treatment of cancer because they can inhibit cancer cell proliferation, tumor angiogenesis, invasiveness and malignant spread of cancerous cells. Many mAbs are in various stages of testing and 11 are currently marketed in the US or Europe for the treatment of cancers that express particular antigens such as human epidermal growth factor receptor-2, CD20, epidermal growth factor receptor and vascular endothelial growth factor. Strategies to conjugate mAbs to toxins, radioactive isotopes and chemotherapeutic drugs to improve efficacy are under intense investigation and numerous immunoconjugates have been studied in the clinical setting. However, the molecules have limitations, and so nanomaterials (NMs), which potentially offer more flexibility of design and functionality in providing platforms for binding of multiple therapeutic agents in a single structure, are being examined as an alternative. Studies utilizing mAb-targeted NMs have shown that they exhibit focused targeting, improved pharmacokinetics and improved "passive" drug delivery via leaky vasculature. Nevertheless, before they can be utilized to treat cancer, potential NM toxicity must be thoroughly investigated. Thus, rigorous testing of NM-mAb conjugates in both in vitro and in vivo systems is underway to determine how NM-mAb conjugates will interact with cells and tissues of the body. In this review, we discuss the broad range of nanomaterials that are under investigation as potential platforms for the presentation of mAbs either as single therapeutics or in combination with other drugs and their advantages and limitations in specifically targeting cancer.
由于单克隆抗体 (mAb) 对单一表位具有极好的特异性，因此它们提供了一种在分子水平上影响细胞功能的手段。特别是，它们在癌症治疗方面具有巨大的应用前景，因为它们可以抑制癌细胞增殖、肿瘤血管生成、侵袭和癌细胞的恶性扩散。许多 mAb 处于不同的测试阶段，目前有 11 种 mAb 在美欧被用于治疗表达特定抗原的癌症，如人类表皮生长因子受体-2、CD20、表皮生长因子受体和血管内皮生长因子。将 mAb 与毒素、放射性同位素和化疗药物偶联以提高疗效的策略正在被深入研究，许多免疫偶联物已在临床环境中进行了研究。然而，这些分子存在局限性，因此纳米材料（NMs）作为替代物正在被研究，其在提供结合多种治疗剂的单一结构平台方面具有更好的设计和功能灵活性。利用 mAb 靶向的 NMs 的研究表明，它们具有靶向性、改善的药代动力学和改善的“被动”药物通过渗漏血管的输送。然而，在将它们用于治疗癌症之前，必须彻底研究潜在的 NM 毒性。因此，正在对 NM-mAb 缀合物进行严格的体外和体内系统测试，以确定 NM-mAb 缀合物将如何与体内细胞和组织相互作用。在这篇综述中，我们讨论了广泛的纳米材料，这些材料被认为是作为单一治疗剂或与其他药物联合使用的 mAb 的潜在载体，讨论了它们在特异性靶向癌症方面的优势和局限性。
