期刊
CHEMICAL SCIENCE
卷 6, 期 12, 页码 7112-7121出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5sc01402f
关键词
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资金
- NIH/NCI [R01CA95142]
- NSF [CHE-0840413]
- NIH Center grant [P30 CA022453]
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.
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