Radionuclide Center, Radiology and Nuclear medicine Amsterdam UMC, VU University, De Boelelaan 1085c, 1081 HV, Amsterdam, the Netherlands.
Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
Chem Rec. 2021 Nov;21(11):3313-3331. doi: 10.1002/tcr.202100182. Epub 2021 Nov 23.
Tumor-associated carbohydrate antigens are overexpressed as altered-self in most common epithelial cancers. Their glycosylation patterns differ from those of healthy cells, functioning as an ID for cancer cells. Scientists have been developing anti-cancer vaccines based on mucin glycopeptides, yet the interplay of delivery system, adjuvant and tumor associated MUC epitopes in the induced immune response is not well understood. The current state of the art suggests that the identity, abundancy and location of the glycans on the MUC backbone are all key parameters in the cellular and humoral response. This review shares lessons learned by us in over two decades of research in glycopeptide vaccines. By bridging synthetic chemistry and immunology, we discuss efforts in designing synthetic MUC1/4/16 vaccines and focus on the role of glycosylation patterns. We provide a brief introduction into the mechanisms of the immune system and aim to promote the development of cancer subunit vaccines.
肿瘤相关碳水化合物抗原在大多数常见的上皮癌中作为自身改变而过度表达。它们的糖基化模式与健康细胞不同，作为癌细胞的 ID。科学家们一直在基于粘蛋白糖肽开发抗癌疫苗，但输送系统、佐剂和肿瘤相关 MUC 表位在诱导免疫反应中的相互作用尚不清楚。目前的研究表明，MUC 主链上聚糖的身份、丰度和位置都是细胞和体液反应的关键参数。这篇综述分享了我们在 20 多年的糖肽疫苗研究中获得的经验教训。通过连接合成化学和免疫学，我们讨论了设计合成 MUC1/4/16 疫苗的努力，并重点讨论了糖基化模式的作用。我们简要介绍了免疫系统的机制，并旨在促进癌症亚单位疫苗的发展。
