A Fully Synthetic Four-Component Antitumor Vaccine Consisting of a Mucin Glycopeptide Antigen Combined with Three Different T-Helper-Cell Epitopes

被引：41

作者：

Palitzsch, Bjoern ^{[1
]}

Hartmann, Sebastian ^{[1
]}

Stergiou, Natascha ^{[2
]}

Glaffig, Markus ^{[1
]}

Schmitt, Edgar ^{[2
]}

Kunz, Horst ^{[1
]}

机构：

[1] Johannes Gutenberg Univ Mainz, Inst Organ Chem, D-55128 Mainz, Germany

[2] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Immunol, D-55101 Mainz, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2014年 / 53卷 / 51期

关键词：

antigen presentation; antitumor vaccines; glycopeptides; T-cell epitopes; tumor cell recognition; B-CELL; IMMUNE-RESPONSES; INDUCTION; PEPTIDES; GLYCOSYLATION; BREAST;

D O I：

10.1002/anie.201406843

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In a new concept of fully synthetic vaccines, the role of T-helper cells is emphasized. Here, a synthetic antitumor vaccine consisting of a diglycosylated tumor-associated MUC1 glycopeptide as the B-cell epitope was covalently cross-linked with three different T-helper-cell epitopes via squaric acid ligation of two linear (glyco) peptides. In mice this four-component vaccine administered without external immunestimulating promoters elicit titers of MUC1-specific antibodies that were about eight times higher than those induced by a vaccine containing only one T-helper-cell epitope. The promising results indicate that multiple activation of different T-helper cells is useful for applications in which increased immunogenicity is required. In personalized medicine, in particular, this flexible construction of a vaccine can serve as a role model, for example, when T-helper-cell epitopes are needed that match human leukocyte antigens (HLA) in different patients.

引用

页码：14245 / 14249

页数：5