Journal
THERANOSTICS
Volume 7, Issue 7, Pages 1942-1952Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.16236
Keywords
DC/tumor fusion cell vaccines; interferon-induced protein-10; folic acid; chitosan
Categories
Funding
- Programs for Changjiang Scholars and Innovative Research Team in University [IRT_15R13]
- National Natural Scientific Foundation of China [81430055, 81372452]
- International Cooperation Project of the Ministry of Science and Technology of China [2015DFA31320]
- Project for Innovative Research Team in Guangxi Natural Science Foundation [2015GXNSFFA-139001]
- Project of Science and Technology of Guangxi [14125008-2-12, 1599005-2-10]
- Science Fund for Distinguished Young Scholars of Guangxi [2012GXNSFFA-060006]
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Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-gamma responses. Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis. Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.
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