Lewis系统抗原的碳水化合物决定簇的三维结构：对有效靶向癌症的抗体的影响。,Immunology and Cell Biology

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Lewis系统抗原的碳水化合物决定簇的三维结构：对有效靶向癌症的抗体的影响。
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2005-11-04 , DOI: 10.1111/j.1440-1711.2005.01374.x
Elizabeth Yuriev ₁ , William Farrugia , Andrew M Scott , Paul A Ramsland

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Lewis系统的碳水化合物抗原已显示在许多上皮细胞起源的癌症中高水平表达，包括结肠癌，乳腺癌，肺癌，前列腺癌和卵巢癌。1型（Le（a）和Le（b））抗原是重要的组织血型，而健康个体中的2型（Le（x）和Le（y））抗原仅以相对较低的水平表达一些组织，包括一些上皮细胞。因此，2型抗原被认为是肿瘤相关抗原，并且是包括基于抗体的免疫疗法在内的癌症治疗的有希望的靶标。在这篇综述中，我们讨论了路易斯寡糖的游离形式和结合形式的构象特征以及与Le（y）和Le（x）抗原复合的抗体的3D结构。总的来说，结构研究表明，路易斯决定簇是刚性结构，通常在自由和结合状态下保持相同的构象。1型和2型Lewis寡糖的刚性性质和形状相似性似乎使其非常适合驱动结构趋同的免疫反应（至少在Le（y）特异性抗体的情况下），以高度特异性地识别单个碳水化合物决定簇，这是开发有效的基于抗体的癌症治疗方法的目标。

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Three-dimensional structures of carbohydrate determinants of Lewis system antigens: implications for effective antibody targeting of cancer.

Lewis system carbohydrate antigens have been shown to be expressed at high levels in many cancers of epithelial cell origin, including those of colon, breast, lung, prostate and ovary. The type 1 (Le(a) and Le(b)) antigens are important histo-blood groups, while type 2 (Le(x) and Le(y)) antigens in healthy individuals are only expressed, at relatively low levels, by a few tissues, including some epithelial cells. Thus, the type 2 antigens are considered to be tumour-associated antigens and are promising targets for cancer treatment, including antibody-based immunotherapy. In this review, we discuss the conformational characteristics of the free and bound forms of Lewis oligosaccharides and the 3D structures of antibodies in complex with Le(y) and Le(x) antigens. Collectively, the structural studies have demonstrated that the Lewis determinants are rigid structures, which generally maintain the same conformation in the free and bound states. The rigid nature and similarities in shape of type 1 and 2 Lewis oligosaccharides appear to make them perfectly suited to driving a structurally convergent immune response (at least in the case of Le(y) specific antibodies) toward a highly specific recognition of individual carbohydrate determinants, which is a goal in the development of effective antibody-based cancer treatments.

更新日期：2019-11-01

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