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

作者：Huang, Zhi-Hua; Shi, Lei; Ma, Jing-Wen; Sun, Zhan-Yi; Cai, Hui; Chen, Yong-Xiang; Zhao, Yu-Fen; Li, Yan-Mei^*

来源：Journal of the American Chemical Society, 2012, 134(21): 8730-8733.

DOI：10.1021/ja211725s

• HUMORAL IMMUNE-RESPONSE
• T-CELL EPITOPE
• ANTICANCER VACCINE
• ANTIGEN
• MOUSE
• IMMUNOTHERAPY
• LIPOPEPTIDES
• RECEPTORS
• INDUCTION
• CHEMISTRY

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.

• 单位
  清华大学