Cancer vaccines using supramolecular hydrogels of NSAID-modified peptides as adjuvants abolish tumorigenesis

Abstract

Inflammatory responses play crucial roles in the development and progression of tumors. Tumor-associated inflammation not only promotes tumor growth but also induces the suppression of immune responses against tumors. We demonstrate in this study that hydrogels of nonsteroidal anti-inflammatory drug (NSAID) modified D-tetrapeptides (G^DF^DF^DY) are promising cancer vaccine adjuvants, especially for Fbp-gel and Car-gel. The hydrogels allow easy incorporation of a protein OVA antigen by vortexing. Our results indicate that vaccines based on Fbp-gel and Car-gel increase IgG production by 1476- and 929-fold, compared with the OVA group, respectively. They exhibit higher IgG2a antibody titers and stimulate the production of IFN-γ and IL-6 cytokines. Their higher antibody and cytokine eliciting properties in combination with their anti-inflammatory properties endow them with excellent tumor elimination properties in vivo. In a preventive immune assay against B16-OVA tumors, they totally prevent tumorigenesis. In a therapeutic immune assay against EG7-OVA tumors, they inhibit tumor growth by 75%, compared with the PBS group. Our results suggest the great potential of our hydrogels in the development of vaccines to treat cancers.