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

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• 作者：Zhi-Hua Huang ; Lei Shi ; Jing-Wen Ma ; Zhan-Yi Sun ; Hui Cai ; Yong-Xiang Chen ; Yu-Fen Zhao ; Yan-Mei Li
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：May 30, 2012
• 年：2012
• 卷：134
• 期：21
• 页码：8730-8733
• 全文大小：222K
• 年卷期：v.134,no.21(May 30, 2012)
• ISSN：1520-5126

文摘

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.