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a Totally Synthetic, Self-Assembling, Adjuvant-Free MUC1 Glycopeptide Vaccine for Cancer Therapy

By Zhi-Hua Huang (1547317), Lei Shi (1235181), Jing-Wen Ma (2079292), Zhan-Yi Sun (1547323), Hui Cai (241921), Yong-Xiang Chen (284449), Yu-Fen Zhao (1547329) and Yan-Mei Li (1547320)

Abstract

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

Topics: Biochemistry, Microbiology, Cell Biology, Genetics, Molecular Biology, Neuroscience, Pharmacology, Biotechnology, Immunology, Cancer, Infectious Diseases, Thr residue, Tn antigen, MUC 1 VNTR, MUC 1 proteins, vaccine candidates, MUC 1 peptide, breast tumor cells, epithelial tumors, vaccine development, level antibody response, Cancer TherapyIn, TACA, cytotoxic T cells, vaccine candidates aggregated, anticancer therapy, PDTRP sequence
Year: 2012
DOI identifier: 10.1021/ja211725s.s001
OAI identifier: oai:figshare.com:article/2518723
Provided by: FigShare
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