Synthetic vaccines consisting of tumor-associated MUC1 glycopeptide antigens and bovine serum albumin
Synthetic vaccines consisting of tumor-associated MUC1 glycopeptide antigens and bovine serum albumin
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DOI：
10.1002/anie.200501593
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Kunz, H
中科院分区：
文献类型：
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作者：
Dziadek, S;Kowalczyk, D;Kunz, H
7624 2005 Wiley-VCH Verlag GmbH & Co. KGaA，魏因海姆Angew. Chem.Int.Ed.2005，44，7624-7630血型[3]，表明不仅糖，而且肽序列，都有助于识别表位。从这一观察我们推断，除了肿瘤相关的糖蛋白，肿瘤选择性肽结构元件是使抗原具有足够的肿瘤选择性所必需的。设计肿瘤选择性糖肽抗原的结构线索来自于对肿瘤相关上皮粘蛋白MUC 1的分析，[4] MUC 1在肿瘤细胞上广泛过表达。MUC 1的细胞外部分含有氨基酸序列HGVTSAPDTRPAPGSTAPPA的许多重复单元。[5]大多数O-糖基化位点位于这些串联重复内。由于葡糖胺基转移酶（C-2GnT-1）的下调和伴随的唾液酸转移酶的过表达，[6]肿瘤细胞上的MUC 1携带短的、过早唾液酸化的糖侧链。用分离自肿瘤组织的MUC 1诱导的抗体[4，5]用于鉴定肽基序PDTRPAP作为MUC 1串联重复序列内的免疫显性表位。[7]用合成的Tn-和T-抗原糖肽验证这些抗MUC 1抗体的特异性。[8，9]此外，饱和转移差NMR分析揭示了来自MUC 1的Tn抗原五肽与单克隆抗体结合的构象。[10个国家]
7624 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2005, 44, 7624–7630 blood groups,[3] indicating that not only the saccharide, but also the peptide sequence, contributed to the recognized epitope. From this observation we inferred that apart from tumor-associated saccharides, tumor-selective peptide structural elements are required to render an antigen sufficiently tumor-selective.Structural leads for the design of tumor-selective glycopeptide antigens are obtained from analyses of the tumorassociated epithelial mucin MUC1,[4] which is extensively over-expressed on tumor cells. The extracellular portion of MUC1 contains numerous repeating units of the amino acid sequence HGVTSAPDTRPAPGSTAPPA.[5] Most O-glycosylation sites are located within these tandem repeats. Owing to the down-regulation of a glucosaminyl transferase (C-2GnT-1) and the concomitant overexpression of sialyl transferases,[6] MUC1 on tumor cells carries short, prematurely sialylated saccharide side chains. Antibodies induced with MUC1 isolated from tumor tissues [4, 5] were used to identify the peptide motif PDTRPAP as an immundominant epitope within the MUC1 tandem repeat.[7] The specificity of these anti-MUC1 antibodies was verified with synthetic Tn-and T-antigen glycopeptides.[8, 9] Moreover, saturation transfer difference NMR analyses revealed the conformation of a Tn antigen pentapeptide from MUC1 bound to a monoclonal antibody.[10]