Cancer stem cells (CSCs) proliferate extensively and drive tumor metastasis and recurrence. CSCs have been identified in over 20 cancer types to date, but it remains unknown how to target and eliminate CSCs in vivo. Aldehyde dehydrogenase (ALDH) is a marker that has been used extensively for isolating CSCs. Here we present a novel approach to target and reduce the frequency of ALDH^high CSCs by vaccination against ALDH. We have identified ALDH1-A1 and ALDH1-A3 epitopes from CSCs and developed synthetic high-density lipoprotein nanodiscs for vaccination against ALDH^high CSCs. Nanodiscs increased antigen trafficking to lymph nodes and generated robust ALDH-specific T cell responses. Nanodisc vaccination against ALDH^high CSCs combined with anti-PD-L1 therapy exerted potent antitumor efficacy and prolonged animal survival in multiple murine models. Overall, this is the first demonstration of a simple nanovaccine strategy against CSCs and may lead to new avenues for cancer immunotherapy against CSCs.

中文翻译：

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通过使用疫苗纳米圆盘靶向癌干细胞进行癌症免疫治疗。

癌症干细胞（CSCs）广泛增殖并推动肿瘤转移和复发。迄今为止，已经在20多种癌症类型中发现了CSC，但是如何在体内靶向和消除CSC仍然未知。醛脱氢酶（ALDH）是一种已广泛用于分离CSC的标记物。在这里，我们提出了一种针对ALDH疫苗的针对性目标并降低ALDH^高CSC频率的新颖方法。我们从CSCs中鉴定了ALDH1-A1和ALDH1-A3表位，并开发了合成的高密度脂蛋白纳米圆片用于ALDH^高CSCs的疫苗接种。纳米圆盘增加了抗原向淋巴结的运输，并产生了强大的ALDH特异性T细胞反应。针对ALDH的纳米光盘疫苗接种率^很高CSC与抗PD-L1疗法的结合在多种小鼠模型中发挥了有效的抗肿瘤功效，并延长了动物的存活率。总体而言，这是针对CSCs的简单纳米疫苗策略的首次展示，可能会为针对CSCs的癌症免疫治疗开辟新途径。