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Issue 12, 2015
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A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity

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Abstract

Therapeutic cancer vaccines based on the abnormal glycans expressed on cancer cells, such as the globo H antigen, have witnessed great progress in recent years. For example, the keyhole limpet hemocyanin (KLH) conjugate of globo H has been on clinical trials as a cancer vaccine. However, such vaccines have intrinsic problems, such as inconsistence in eliciting T cell-mediated immunity in cancer patients and difficult quality control. To address the issue, a structurally defined fully synthetic glycoconjugate vaccine composed of globo H and monophosphoryl lipid A (MPLA) was developed. The new vaccine was shown to elicit robust IgG1 antibody responses and T cell-dependent immunity, which is desired for anticancer vaccines, and induce significantly faster and stronger immune responses than the globo H–KLH conjugate. Moreover, it was self-adjuvanting, namely, inducing immune responses without the use of an external adjuvant, thus MPLA was not only a vaccine carrier but also a build-in adjuvant. It was also found that antibodies induced by the new vaccine could selectively bind to and mediate strong complement-dependent cytotoxicity to globo H-expressing MCF-7 cancer cell. All of the results have demonstrated that the globo H–MPLA conjugate is a better cancer vaccine than the globo H–KLH conjugate under experimental conditions and is worth further investigation and development.

Graphical abstract: A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity

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Publication details

The article was received on 17 apr. 2015, accepted on 09 sep. 2015 and first published on 22 sep. 2015


Article type: Edge Article
DOI: 10.1039/C5SC01402F
Citation: Chem. Sci., 2015,6, 7112-7121
  • Open access: Creative Commons BY license
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    A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity

    Z. Zhou, G. Liao, S. S. Mandal, S. Suryawanshi and Z. Guo, Chem. Sci., 2015, 6, 7112
    DOI: 10.1039/C5SC01402F

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