Injectable cryogel-based whole-cell cancer vaccines.
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.
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.
Sidi A
SA
Bencherif
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.
R
R
Warren Sands
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.
Omar A
OA
Ali
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.
Weiwei A
WA
Li
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.
Sarah A
SA
Lewin
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] School of Engineering, LMIS4, Station 17, École polytechnique fédérale de Lausanne, Lausanne 1015, Switzerland.
Thomas M
TM
Braschler
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.
Ting-Yu
TY
Shih
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.
Catia S
CS
Verbeke
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.
Deen
D
Bhatta
Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Glenn
G
Dranoff
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.
David J
DJ
Mooney
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D059985:Cryogels / Q000737:chemistry*; D003713:Dendritic Cells; D005260:Female; D008545:Melanoma / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D013601:T-Lymphocytes
D019496:Cancer Vaccines; D059985:Cryogels