Fully synthetic Mincle-dependent self-adjuvanting cancer vaccines elicit robust humoral and T cell-dependent immune responses and protect mice from tumor development.
Fully synthetic Mincle-dependent self-adjuvanting cancer vaccines elicit robust humoral and T cell-dependent immune responses and protect mice from tumor development.
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全合成的 Mincle 依赖性自我辅助癌症疫苗可引发强大的体液和 T 细胞依赖性免疫反应，并保护小鼠免受肿瘤发展
DOI：
10.1039/d1sc05736g
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发表时间：
2021-12-15
期刊：
影响因子：
8.4
通讯作者：
Liao G
中科院分区：
文献类型：
--
作者：
Luo X;Lian Q;Li W;Chen L;Zhang R;Yang D;Gao L;Qi X;Liu Z;Liao G
建立了一种基于巨噬细胞诱导的C型凝集素（Mincle）激动剂的新策略来构建合成的癌症疫苗。以唾液酸-Tn（STn）为模型抗原，通过简单有效的方法设计并合成了四种以Mincle激动剂为内置佐剂的缀合物。所有缀合物都可以以Mincle依赖性方式诱导BMDM产生炎性细胞因子，并且发现在小鼠中单独引起强烈的体液和T细胞依赖性免疫应答。相应的抗体可以识别、结合并对STn阳性癌细胞表现出补体依赖性细胞毒性，导致肿瘤细胞溶解。此外，所有偶联物均能有效抑制肿瘤生长，延长小鼠体内存活时间，治疗效果优于STn-CRM 197/Al。值得注意的是，与常规糖蛋白偶联物疫苗相比，这些全合成偶联物疫苗不会引起“表位抑制”。因此，Mincle配体作为开发具有用于癌症治疗的自佐剂性质的新疫苗载体的平台具有巨大的潜力。初步的构效关系分析表明，一个疫苗含有一个STn抗原进行vizantin表现出最好的效果，提供支持的进一步优化和额外的研究Mincle激动剂作为载体的自我辅助癌症疫苗。建立了一种基于巨噬细胞诱导的C型凝集素（Mincle）激动剂的新策略来构建合成的癌症疫苗。
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. A new strategy based on a Macrophage-inducible C-type lectin (Mincle) agonist was established to construct synthetic cancer vaccines.
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影响因子：
2.1
作者：
Khan, Ayesha;Kodar, Kristel;Stocker, Bridget L.
通讯作者：
Stocker, Bridget L.
影响因子：
8.4
作者：
Ghosh S;Trabbic KR;Shi M;Nishat S;Eradi P;Kleski KA;Andreana PR
通讯作者：
Andreana PR
影响因子：
11.5
作者：
Gilewski, Teresa A.;Ragupathi, Govind;Livingston, Philip O.
通讯作者：
Livingston, Philip O.
影响因子：
4.3
作者：
Buskas, T;Li, YH;Boons, GJ
通讯作者：
Boons, GJ
影响因子：
7.3
作者：
Broecker, Felix;Goetze, Sebastian;Seeberger, Peter H.
通讯作者：
Seeberger, Peter H.