Academic Department of Clinical Oncology, City Hospital Campus, University of Nottingham, Nottingham, NG5 1PB, UK.
Future Oncol. 2012 Aug;8(8):943-60. doi: 10.2217/fon.12.88.
Glycans represent a vast class of molecules that modify either proteins or lipids. They exert and regulate important and complex functions in both normal and cancer cell metabolism. As such, the most immunogenic glycans have been targeted in passive and active immunotherapy in human cancer for the past 25 years but it is only recently that techniques have become available to uncover novel glycan targets. The main focus of this review article is to highlight why and how monoclonal antibodies (mAbs) recognizing glycans, and in particular the glycans expressed on glycolipids, are being used in various strategies to target and kill cancer cells. The article reports on the historical use of mAbs and on very recent progress made in antitumor therapy using the anti-GD2 mAb and the antiganglioside mAbs, anti-N-glycolylneuraminic acid mAb and anti-Lewis mAb. Anti-GD2 is showing great promise in Phase III clinical trials in adjuvant treatment of neuroblastoma. Racotumomab, an anti-idiotypic mAb mimicking N-glycolylneuraminic acid-containing gangliosides, is currently being tested in a randomized, controlled Phase II/III clinical trial. This article also presents various strategies used by different groups to develop mAbs against these naturally poorly immunogenic glycans.
糖链是一大类能够修饰蛋白质或脂质的分子。它们在正常细胞和癌细胞代谢中发挥着重要而复杂的作用，并进行着调节。因此，在过去的 25 年中，人们一直在针对最具免疫原性的糖链，开展被动和主动免疫疗法来治疗人类癌症，但直到最近，才出现了揭示新型糖链靶点的技术。本文的主要重点是，强调为什么以及如何使用识别糖链的单克隆抗体（mAbs），特别是识别糖脂上糖链的 mAbs，用于各种策略来靶向和杀死癌细胞。本文报告了 mAbs 的历史应用，以及最近在使用抗 GD2 mAb 和抗神经节苷脂 mAbs、抗 N-糖酰基神经氨酸 mAb 和抗 Lewis mAb 的抗肿瘤治疗方面取得的进展。抗 GD2 在神经母细胞瘤辅助治疗的 III 期临床试验中显示出巨大的前景。Racotumomab 是一种抗独特型 mAb，模拟含有 N-糖酰基神经氨酸的神经节苷脂，目前正在一项随机、对照的 II/III 期临床试验中进行测试。本文还介绍了不同研究小组为开发针对这些天然免疫原性较差的糖链的 mAbs 而采用的各种策略。
