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Fully Synthetic Self-Adjuvanting Thioether-Conjugated Glycopeptide[BOND]Lipopeptide Antitumor Vaccines for the Induction of Complement-Dependent Cytotoxicity against Tumor Cells

Authors

  • Dr. Hui Cai,

    1. Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (P.R. China)
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  • Zhan-Yi Sun,

    1. Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (P.R. China)
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  • Zhi-Hua Huang,

    1. Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (P.R. China)
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  • Lei Shi,

    1. Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (P.R. China)
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  • Prof. Dr. Yu-Fen Zhao,

    1. Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (P.R. China)
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  • Prof. Dr. Horst Kunz,

    Corresponding author
    1. Institute of Organic Chemistry, Johannes Gutenberg University of Mainz, Duesbergweg 10-14, 55128 Mainz (Germany)
    • Institute of Organic Chemistry, Johannes Gutenberg University of Mainz, Duesbergweg 10-14, 55128 Mainz (Germany)
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  • Prof. Dr. Yan-Mei Li

    Corresponding author
    1. Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (P.R. China)
    • Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (P.R. China)
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Abstract

Glycopeptides of tumor-associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune-response-stimulating T-cell epitopes and the Pam3Cys lipopeptide to induce strong immune responses in mice. A new thioether-ligation method for the synthesis of two- and three-component vaccines that contain MUC1 glycopeptides as the B-cell epitopes, a T-cell epitope peptide, and the Pam3CSK4 lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund′s adjuvant or in aqueous PBS buffer. The three-component vaccines that contained the Tetanus Toxoid P2 T-cell epitope peptide induced strong immune responses, even when administered just in PBS. By activation of the complement-dependent cytotoxicity (CDC) complex, the antisera induced the killing of tumor cells.

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