Bencherif Sidi A, Warren Sands R, Ali Omar A, Li Weiwei A, Lewin Sarah A, Braschler Thomas M, Shih Ting-Yu, Verbeke Catia S, Bhatta Deen, Dranoff Glenn, Mooney David J
1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA [3] Sorbonne University, UTC CNRS UMR 7338, Biomechanics and Bioengineering (BMBI), University of Technology of Compiègne, BP 20529, Rue Personne de Roberval, Compiègne 60205, France.
1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA [3] University of Pittsburgh Medical Center Department of Medicine, Pittsburgh, Pennsylvania 15232, USA.
Nat Commun. 2015 Aug 12;6:7556. doi: 10.1038/ncomms8556.
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 tumour 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 tumour 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-tumour 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.
一种基于生物材料的疫苗接种系统,该系统使用最少的体外操作,可在原位增加树突状细胞(DC)数量,提供DC与移植肿瘤细胞相互作用的物理空间以及免疫原性环境。在此,我们将作为DC增强因子的GM-CSF和作为DC激活因子的CpG ODN封装到海绵状大孔冷冻凝胶中。将这些冷冻凝胶皮下注射到小鼠体内,以定位移植的肿瘤细胞,并以可控的时空方式递送免疫调节因子。在黑色素瘤模型中,这些疫苗引发了由常规DC和浆细胞样DC组成的局部浸润,随后诱导了强效、持久且特异性的抗肿瘤T细胞反应。这些冷冻凝胶可以通过微创方式递送,无需对移植癌细胞进行基因改造,并能持续释放免疫调节剂。总之,这些发现表明冷冻凝胶有潜力作为癌细胞疫苗接种的平台。