Dingjan Tamir, Spendlove Ian, Durrant Lindy G, Scott Andrew M, Yuriev Elizabeth, Ramsland Paul A
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Academic Department of Clinical Oncology, Division of Cancer and Stem cells, University of Nottingham, City Hospital, Nottingham NG5 1PB, United Kingdom.
Mol Immunol. 2015 Oct;67(2 Pt A):75-88. doi: 10.1016/j.molimm.2015.02.028. Epub 2015 Mar 7.
Monoclonal antibodies represent the most successful class of biopharmaceuticals for the treatment of cancer. Mechanisms of action of therapeutic antibodies are very diverse and reflect their ability to engage in antibody-dependent effector mechanisms, internalize to deliver cytotoxic payloads, and display direct effects on cells by lysis or by modulating the biological pathways of their target antigens. Importantly, one of the universal changes in cancer is glycosylation and carbohydrate-binding antibodies can be produced to selectively recognize tumor cells over normal tissues. A promising group of cell surface antibody targets consists of carbohydrates presented as glycolipids or glycoproteins. In this review, we outline the basic principles of antibody-based targeting of carbohydrate antigens in cancer. We also present a detailed structural view of antibody recognition and the conformational properties of a series of related tissue-blood group (Lewis) carbohydrates that are being pursued as potential targets of cancer immunotherapy.
单克隆抗体是治疗癌症最为成功的一类生物制药。治疗性抗体的作用机制多种多样，体现了它们参与抗体依赖性效应机制、内化以递送细胞毒性载荷以及通过裂解或调节其靶抗原的生物学途径对细胞产生直接作用的能力。重要的是，癌症的普遍变化之一是糖基化，可产生碳水化合物结合抗体以选择性地识别肿瘤细胞而非正常组织。一组有前景的细胞表面抗体靶点由以糖脂或糖蛋白形式呈现的碳水化合物组成。在本综述中，我们概述了基于抗体靶向癌症中碳水化合物抗原的基本原理。我们还详细介绍了抗体识别的结构观点以及一系列相关组织血型（刘易斯）碳水化合物的构象特性，这些碳水化合物正被作为癌症免疫治疗的潜在靶点进行研究。
