Abstract
IL-15 has been actively investigated for its potential in tumor immunotherapy. To enhance the anti-tumor activity of IL-15, the novel PFC-1 construct was designed, which comprises the following 3 parts: (1) IL-15Rα fused with IL-15 to enhance IL-15 activity, (2) an Fc fragment to increase protein half-life, and (3) an integrin-targeting RGD peptide to enhance tumor targeting. PFC-1 showed tumor cell targeting without compromising IL-15 activity. PFC-1 also had potent anti-tumor activities in xenograft models, suggesting the potential application of this multi-functional fusion protein in tumor therapy.
Keywords:
IL-15; IL-15Rα; RGD; fusion protein; tumor immunotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology*
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Animals
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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Human Umbilical Vein Endothelial Cells / drug effects
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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Integrin alphaVbeta3 / metabolism
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / physiology
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Lung Neoplasms / prevention & control*
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Lung Neoplasms / secondary
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Melanoma, Experimental / drug therapy*
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Melanoma, Experimental / secondary
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Mice, Inbred C57BL
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Molecular Targeted Therapy
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Neoplasm Transplantation
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Recombinant Fusion Proteins / pharmacology*
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Skin Neoplasms / drug therapy*
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Skin Neoplasms / pathology
Substances
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Adjuvants, Immunologic
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Antineoplastic Agents
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Integrin alphaVbeta3
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PFC-1 peptide
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Recombinant Fusion Proteins