Injectable cryogel-based whole-cell cancer vaccines.
Injectable cryogel-based whole-cell cancer vaccines.
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可注射冷冻凝胶的全细胞癌疫苗。
DOI：
10.1038/ncomms8556
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发表时间：
2015-08-12
影响因子：
16.6
通讯作者：
Mooney DJ
中科院分区：
文献类型：
--
作者：
Bencherif SA;Warren Sands R;Ali OA;Li WA;Lewin SA;Braschler TM;Shih TY;Verbeke CS;Bhatta D;Dranoff G;Mooney DJ
使用最小体外操作的基于生物材料的疫苗接种系统可以提供树突状细胞（DC）数量的原位增强、DC与移植的肿瘤细胞界面的物理空间以及免疫原性环境。在这里，我们封装GM-CSF，作为DC增强因子，和CpG ODN，作为DC激活因子，到海绵状大孔冻凝胶。这些冷冻凝胶被皮下注射到小鼠体内，以定位移植的肿瘤细胞，并以受控的时空方式递送免疫调节因子。这些疫苗引发由常规和浆细胞样DC组成的局部浸润，随后在黑色素瘤模型中诱导有效、持久和特异性的抗肿瘤T细胞应答。这些冷冻凝胶可以以微创方式递送，绕过对移植癌细胞的遗传修饰的需要，并提供免疫调节剂的持续释放。总而言之，这些发现表明冷冻凝胶有可能作为癌细胞疫苗接种的平台。
A biomaterial-based vaccination system that uses minimal extracorporeal manipulation could provide in situ enhancement of dendritic cell (DC) numbers, a physical space where DCs interface with transplanted tumor cells, and an immunogenic context. Here we encapsulate GM-CSF, serving as a DC enhancement factor, and CpG ODN, serving as a DC activating factor, into sponge-like macroporous cryogels. These cryogels are injected subcutaneously into mice to localize transplanted tumor cells and deliver immunomodulatory factors in a controlled spatio-temporal manner. These vaccines elicit local infiltrates composed of conventional and plasmacytoid DCs, with the subsequent induction of potent, durable, and specific anti-tumor T cell responses in a melanoma model. These cryogels can be delivered in a minimally invasive manner, bypass the need for genetic modification of transplanted cancer cells, and provide sustained release of immunomodulators. Altogether, these findings indicate the potential for cryogels to serve as a platform for cancer cell vaccinations.