Injectable cryogel-based whole-cell cancer vaccines

被引:367
作者
Bencherif, Sidi A. [1 ,2 ,3 ]
Sands, R. Warren [1 ,2 ,4 ]
Ali, Omar A. [1 ,2 ]
Li, Weiwei A. [1 ,2 ]
Lewin, Sarah A. [1 ,2 ]
Braschler, Thomas M. [1 ,2 ,5 ]
Shih, Ting-Yu [1 ,2 ]
Verbeke, Catia S. [1 ,2 ]
Bhatta, Deen [1 ,2 ]
Dranoff, Glenn [6 ,7 ,8 ,9 ]
Mooney, David J. [1 ,2 ]
机构
[1] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[2] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
[3] Univ Technol Compiegne, Univ Sorbonne, UTC CNRS UMR 7338, Biomech & Bioengn BMBI, F-60205 Compiegne, France
[4] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15232 USA
[5] Ecole Polytech Fed Lausanne, Stn 17, LMIS4, Sch Engn, CH-1015 Lausanne, Switzerland
[6] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA
[7] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA
[8] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA
[9] Harvard Univ, Sch Med, Boston, MA 02215 USA
基金
瑞士国家科学基金会; 美国国家卫生研究院;
关键词
COLONY-STIMULATING FACTOR; DENDRITIC CELLS; PHASE-I; GM-CSF; SAFETY; IMMUNOTHERAPY; MELANOMA; RESPONSES; ANTIBODY; VACCINATION;
D O I
10.1038/ncomms8556
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
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页数:13
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