Abstract
We utilized the gene gun to transfect subcutaneous D5 melanoma and MT-901 mammary carcinoma tumors in situ with a granulocyte/macrophage-colony-stimulating factor (GM-CSF) plasmid complexed to gold particles. There was diminished tumor growth following bombardment with GM-CSF plasmid, which was apparent only during the period of administration. Transgenic GM-CSF was produced by the skin overlying the tumors and not by the tumors themselves. GM-CSF plasmid bombardment resulted in increased cell yields within tumor-draining lymph nodes (TDLN) with at least a 12-fold increase in the percentage of dendritic cells (8.9%) compared to controls (0. 7%). Secondarily activated TDLN cells from animals transfected with GM-CSF demonstrated enhanced cytokine release (interferon gamma, GM-CSF and interleukin-10) in response to tumor stimulator cells compared to controls, and had an increased capacity to mediate tumor regression in adoptive immunotherapy. There was a small, but detectable, non-specific immune adjuvant effect observed with gold particle bombardment alone, which was less than with GM-CSF plasmid. The adjuvant effect of GM-CSF plasmid required peri-tumoral transgene expression since gene bombardment away from the tumor was ineffective.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biolistics*
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Cytokines / metabolism*
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Dendritic Cells / immunology
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Female
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Gene Expression Regulation
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Genetic Therapy / methods*
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Gold
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Immunotherapy, Adoptive*
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Interferon-gamma / metabolism
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Interleukin-10 / metabolism
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Lymph Nodes / immunology*
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Lymph Nodes / pathology
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Lymphocyte Count
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Mammary Neoplasms, Experimental / immunology
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Mammary Neoplasms, Experimental / therapy*
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Melanoma, Experimental / immunology
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Melanoma, Experimental / therapy*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Particle Size
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Plasmids / administration & dosage*
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Plasmids / therapeutic use
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / pharmacology
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Skin / metabolism*
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Skin Neoplasms / immunology
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Skin Neoplasms / therapy*
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Transfection / methods
Substances
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Cytokines
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Recombinant Fusion Proteins
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Interleukin-10
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Gold
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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor