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

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 vaccin...

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Autores principales: Zhou, Zhifang, Liao, Guochao, Mandal, Satadru S., Suryawanshi, Sharad, Guo, Zhongwu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762603/
https://www.ncbi.nlm.nih.gov/pubmed/26918109
http://dx.doi.org/10.1039/c5sc01402f
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author Zhou, Zhifang
Liao, Guochao
Mandal, Satadru S.
Suryawanshi, Sharad
Guo, Zhongwu
author_facet Zhou, Zhifang
Liao, Guochao
Mandal, Satadru S.
Suryawanshi, Sharad
Guo, Zhongwu
author_sort Zhou, Zhifang
collection PubMed
description 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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spelling pubmed-47626032016-06-01 A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity Zhou, Zhifang Liao, Guochao Mandal, Satadru S. Suryawanshi, Sharad Guo, Zhongwu Chem Sci Chemistry 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. Royal Society of Chemistry 2015-12-01 2015-09-22 /pmc/articles/PMC4762603/ /pubmed/26918109 http://dx.doi.org/10.1039/c5sc01402f Text en This journal is © The Royal Society of Chemistry 2015 http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Zhou, Zhifang
Liao, Guochao
Mandal, Satadru S.
Suryawanshi, Sharad
Guo, Zhongwu
A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity
title A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity
title_full A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity
title_fullStr A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity
title_full_unstemmed A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity
title_short A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity
title_sort fully synthetic self-adjuvanting globo h-based vaccine elicited strong t cell-mediated antitumor immunity
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762603/
https://www.ncbi.nlm.nih.gov/pubmed/26918109
http://dx.doi.org/10.1039/c5sc01402f
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