Injectable cryogel-based whole-cell cancer vaccines

Sidi A. Bencherif, R. Warren Sands, Omar A. Ali, Weiwei A. Li, Sarah A. Lewin, Thomas M. Braschler, Ting-Yu Shih, Catia S. Verbeke, Deen Bhatta, Glenn Dranoff and David J. Mooney ()
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Sidi A. Bencherif: School of Engineering and Applied Sciences, Harvard University
R. Warren Sands: School of Engineering and Applied Sciences, Harvard University
Omar A. Ali: School of Engineering and Applied Sciences, Harvard University
Weiwei A. Li: School of Engineering and Applied Sciences, Harvard University
Sarah A. Lewin: School of Engineering and Applied Sciences, Harvard University
Thomas M. Braschler: School of Engineering and Applied Sciences, Harvard University
Ting-Yu Shih: School of Engineering and Applied Sciences, Harvard University
Catia S. Verbeke: School of Engineering and Applied Sciences, Harvard University
Deen Bhatta: School of Engineering and Applied Sciences, Harvard University
Glenn Dranoff: Brigham and Women’s Hospital and Harvard Medical School
David J. Mooney: School of Engineering and Applied Sciences, Harvard University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms8556

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