Abstract
We have recently demonstrated that a 4-in-1 gene therapy strategy that contains two anti-angiogenic genes [endostatin and pigment epithelium-derived factor] and two cytokine genes [granulocyte macrophage colony-stimulating factor and interleukin 12] has a considerable antitumor effect on large tumors in a woodchuck hepatoma model. The current study further investigates the underlying mechanisms for the antitumor effect observed by using small rodent models. We found that immunotherapy alone increased immunosuppressive cells in large tumors over time, whereas the anti-angiogenic therapy contained in the 4-in-1 strategy alleviated immunosuppression and made tumors vulnerable to immunotherapy, thus resulting in a synergistic antitumor effect.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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Cell Line, Tumor
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Combined Modality Therapy
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Endostatins / biosynthesis
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Endostatins / genetics*
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Endostatins / immunology*
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Eye Proteins / biosynthesis
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Eye Proteins / genetics*
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Eye Proteins / immunology*
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Genetic Therapy / methods*
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Humans
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Immunotherapy / methods*
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Liver Neoplasms, Experimental / blood supply
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Liver Neoplasms, Experimental / genetics
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Liver Neoplasms, Experimental / immunology
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Liver Neoplasms, Experimental / therapy*
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Lymphocytes, Tumor-Infiltrating / immunology
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Mice
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Mice, Inbred BALB C
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / immunology
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Neovascularization, Pathologic / therapy
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Nerve Growth Factors / biosynthesis
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Nerve Growth Factors / genetics*
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Nerve Growth Factors / immunology*
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Serpins / biosynthesis
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Serpins / genetics*
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Serpins / immunology*
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T-Lymphocytes, Regulatory / immunology
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Tumor Microenvironment / immunology
Substances
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Endostatins
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Eye Proteins
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Nerve Growth Factors
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Serpins
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pigment epithelium-derived factor