A targeted IL-15 fusion protein with potent anti-tumor activity

Cancer Biol Ther. 2015;16(9):1415-21. doi: 10.1080/15384047.2015.1071739. Epub 2015 Jul 15.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / physiology
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / secondary
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy
  • Neoplasm Transplantation
  • Recombinant Fusion Proteins / pharmacology*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Integrin alphaVbeta3
  • PFC-1 peptide
  • Recombinant Fusion Proteins