A totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine for cancer therapy.

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.

• Authors: Zhi-Hua Huang, Lei Shi, Jing-Wen Ma, Zhan-Yi Sun, Hui Cai, Yong-Xiang Chen, Yu-Fen Zhao, Yan-Mei Li
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 134 Issue 21 Pg. 8730-3 (May 30 2012) ISSN: 1520-5126 [Electronic] United States
• PMID: 22587010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Mucin-1
• Peptide Fragments

Topics

• Amino Acid Sequence
• Cancer Vaccines (chemical synthesis, chemistry, immunology)
• Cell Line, Tumor
• Drug Design
• Humans
• Microsatellite Repeats
• Molecular Sequence Data
• Mucin-1 (chemistry, genetics)
• Neoplasms (immunology, pathology, therapy)
• Peptide Fragments (chemical synthesis, chemistry, immunology)
• Protein Multimerization
• Protein Structure, Tertiary