Injectable, Tough Alginate Cryogels as Cancer Vaccines

Ting‐Yu Shih; Serena O. Blacklow; Aileen W. Li; Benjamin R. Freedman; Sidi Bencherif; Sandeep T. Koshy; Max C. Darnell; David J. Mooney

Index: 10.1002/adhm.201701469

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Abstract

A covalently crosslinked methacrylated (MA)‐alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA‐alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked‐only cryogels break after injection. Cytosine‐phosphodiester‐guanine (CpG)‐delivering tough cryogels effectively activate dendritic cells (DCs). Granulocyte macrophage colony‐stimulating factor releasing tough cryogels recruit four times more DCs than blank gels by day 7 in vivo. The tough cryogel vaccine induces strong antigen‐specific cytotoxic T‐lymphocyte and humoral responses. These vaccines prevent tumor formation in 80% of mice inoculated with HER2/neu‐overexpressing DD breast cancer cells. The MA‐alginate tough cryogels provide a promising minimally invasive delivery platform for cancer vaccinations.