Zhu Jianglong, Wan Qian, Ragupathi Govind, George Constantine M, Livingston Philip O, Danishefsky Samuel J
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 YorkAVenue, New York, New York 10065, USA.
J Am Chem Soc. 2009 Mar 25;131(11):4151-8. doi: 10.1021/ja810147j.
Carbohydrate and peptide-based antitumor vaccine constructs featuring clusters of both tumor associated carbohydrate antigens and mucin-like peptide epitopes have been designed, synthesized, and studied. The mucin-based epitopes are included to act, potentially, as T-cell epitopes in order to provoke a strong immune response. Hopefully the vaccine will simulate cell surface architecture, thereby provoking levels of immunity against cancer cell types displaying such characteristics. With this central idea in mind, we designed a new vaccine type against ovarian cancer. Following advances in glycohistology, our design is based on clusters of Gb(3) antigen and also incorporates a MUC5AC peptide epitope. The vaccine is among the most complex targeted constructs to be assembled by chemical synthesis to date. The strategy for the synthesis employed a Gb(3)-MUC5AC thioester cassette as a key building block. Syntheses of both nonconjugate and KLH-conjugated vaccines constructs have been accomplished.
具有肿瘤相关碳水化合物抗原簇和粘蛋白样肽表位簇的基于碳水化合物和肽的抗肿瘤疫苗构建体已被设计、合成和研究。包含基于粘蛋白的表位，其可能作为T细胞表位起作用，以引发强烈的免疫反应。有望该疫苗将模拟细胞表面结构，从而激发针对显示此类特征的癌细胞类型的免疫水平。基于这一核心思想，我们设计了一种针对卵巢癌的新型疫苗。随着糖组织学的进展，我们的设计基于Gb(3)抗原簇，并且还纳入了MUC5AC肽表位。该疫苗是迄今为止通过化学合成组装的最复杂的靶向构建体之一。合成策略采用Gb(3)-MUC5AC硫酯盒作为关键构建块。已完成非缀合和KLH缀合疫苗构建体的合成。
