A cancer vaccine based on the marine antimicrobial peptide pardaxin (GE33) for control of bladder-associated tumors

Abstract

The marine antimicrobial peptide (AMP) GE33, also known as pardaxin, possesses antimicrobial and anticancer properties, and modulates host signaling. GE33 has cytotoxic effects on murine bladder carcinoma (MBT-2) cells. Here, we investigated the potential of GE33 combined with inactivated MBT-2 as a cancer vaccine. The presence of up to 12.5 μg of GE33 did not inhibit the proliferation or endogenous nitrous oxide (NO) levels of RAW264.7 cells. However, the secretion of MCP-1, IL-6, and IL-12 by RAW264.7 cells was affected by GE33. We proceeded to test the effectiveness of the vaccine by immunizing mice at 7, 14, and 21 days of age, and injecting live MBT-2 cells on the 28th day. Tumor growth by the 58th day was attenuated in mice treated with the vaccine, as compared to the control group. Induction of MBT-2 specific-tumor antigens was increased in mice immunized with our vaccine. Furthermore, activation of T-cell receptors, cytotoxic T-cells, and NK cells was enhanced, and these showed high specificity for targeting tumor cells. Finally, immunization controlled excess recruitment of monocytes, lymphocytes, T-helper cells, and NK cells, and decreased the expression of VEGF. This report provides empirical evidence that our GE33-based vaccine enhances antitumor immunity in mice.