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

Nanoscale. 2017 Sep 28;9(37):14058-14064. doi: 10.1039/c7nr04990k.

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 (GDFDFDY) 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.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cancer Vaccines / pharmacology*
  • Carcinogenesis / drug effects*
  • Female
  • Humans
  • Hydrogels*
  • Melanoma, Experimental / drug therapy
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / drug therapy
  • Ovalbumin
  • Peptides / pharmacology*

Substances

  • Adjuvants, Immunologic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cancer Vaccines
  • Hydrogels
  • Peptides
  • Ovalbumin