期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 134, 期 21, 页码 8730-8733出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja211725s
关键词
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资金
- Major State Basic Research Development Program of China (973 Program) [2012CB821600]
- National Natural Science Foundation of China [20825206, 21028004]
- Sino-German Center for Research Promotion [GZ561]
In the development of vaccines for epithelial tumors, the key targets are MUC1 proteins, which have a variable number of tandem repeats (VNTR) bearing tumor-associated carbohydrate antigens (TACAs), such as Tn and STn. A major obstacle in vaccine development is the low immunogenicity of the short MUC1 peptide. To overcome this obstacle, we designed, synthesized, and evaluated several totally synthetic self-adjuvanting vaccine candidates with self-assembly domains. These vaccine candidates aggregated into fibrils and displayed multivalent B-cell epitopes under mild conditions. Glycosylation of Tn antigen on the Thr residue of PDTRP sequence in MUC1 VNTR led to effective immune response. These vaccines elicited a high level antibody response without any adjuvant and induced antibodies that recognized human breast tumor cells. These vaccines appeared to act through a T-cell independent pathway and were associated with the activation of cytotoxic T cells. These fully synthetic, molecularly defined vaccine candidates had several features that hold promise for anticancer therapy.
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