Fully synthetic Mincle-dependent self-adjuvanting cancer vaccines elicit robust humoral and T cell-dependent immune responses and protect mice from tumor development,Chemical Science

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Fully synthetic Mincle-dependent self-adjuvanting cancer vaccines elicit robust humoral and T cell-dependent immune responses and protect mice from tumor development
Chemical Science ( IF 7.6 ) Pub Date : 2021-12-01 , DOI: 10.1039/d1sc05736g
Xiang Luo ₁ , Qinghai Lian ₁ , Wenwei Li ₁ , Liqing Chen ₁ , Renyu Zhang ₁ , Deying Yang ₁ , Lingqiang Gao ₁ , Xiaoxiao Qi ₁ , Zhongqiu Liu ₁ , Guochao Liao ₁

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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.

中文翻译：

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

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癌症疫苗。使用唾液酸-Tn (STn) 作为模型抗原，通过简单有效的方法设计并合成了四种以 Mincle 激动剂作为内置佐剂的缀合物。所有缀合物都能诱导 BMDM 以 Mincle 依赖性方式产生炎性细胞因子，并且发现仅在小鼠中即可引发强烈的体液和 T 细胞依赖性免疫反应。相应的抗体可以识别、结合 STn 阳性癌细胞并表现出补体依赖性细胞毒性，导致肿瘤细胞裂解。而且，所有缀合物都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-CRM197/Al。值得注意的是，与传统的糖蛋白结合疫苗相比，这些全合成结合疫苗不会引起“表位抑制”。因此，Mincle 配体作为开发具有自我辅助癌症治疗特性的新型疫苗载体的平台具有巨大的潜力。初步构效关系分析表明，含有Vizantin携带的一种STn抗原的疫苗表现出最佳功效，为进一步优化和进一步研究Mincle激动剂作为自身辅助癌症疫苗的载体提供了支持。

更新日期：2021-12-01

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