期刊
CHEMICAL SCIENCE
卷 12, 期 48, 页码 15998-16013出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1sc05736g
关键词
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资金
- National Natural Science Foundation of China [81773580, 82003594]
- Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme
- Department of Education of Guangdong Province, China [2020KZDZX1057, 2020KQNCX016]
- Science and Technology Planning Program of Guangzhou City, China [202008040004]
- Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine [2018B030322011]
The strategy of using Mincle agonist with STn antigen conjugates shows promising results in inducing robust immune responses and inhibiting tumor growth, demonstrating the potential for developing new vaccine carriers with self-adjuvanting properties for cancer treatment.
A new strategy based on a macrophage-inducible C-type lectin (Mincle) agonist was established to construct synthetic cancer vaccines. Using sialyl-Tn (STn) as a model antigen, four conjugates with the Mincle agonist as a built-in adjuvant were designed and synthesized through a facile and efficient method. All conjugates could induce BMDMs to produce inflammatory cytokines in a Mincle-dependent manner and were found to elicit robust humoral and T cell-dependent immune responses alone in mice. The corresponding antibodies could recognize, bind and exhibit complement-dependent cytotoxicity to STn-positive cancer cells, leading to tumor cell lysis. Moreover, all conjugates could effectively inhibit tumor growth and prolong the mice survival time in vivo, with therapeutic effects better than STn-CRM197/Al. Notably, compared to conventional glycoprotein conjugate vaccines, these fully synthetic conjugate vaccines do not cause epitope suppression. Mincle ligands thus hold great potential as a platform for the development of new vaccine carriers with self-adjuvanting properties for cancer treatment. Preliminary structure-activity relationship analysis shows that a vaccine containing one STn antigen carried by vizantin exhibits the best efficacy, providing support for further optimization and additional investigation into Mincle agonists as the carrier of self-adjuvanting cancer vaccines.
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