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A cancer vaccine based on the marine antimicrobial peptide pardaxin (GE33) for control of bladder-associated tumors
Authors:Han-Ning Huang  Venugopal Rajanbabu  Chieh-Yu Pan  Yi-Lin Chan  Chang-Jer Wu  Jyh-Yih Chen
Affiliation:1. Department of Food Science, National Taiwan Ocean University, 2, Pei-Ning Road, Keelung, Taiwan;2. Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Road, Jiaushi, Ilan 262, Taiwan;3. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
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.
Keywords:Pardaxin   Antimicrobial peptide   MBT-2   Bladder tumor   Cancer vaccine   Cytokines
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