Fusion protein from RGD peptide and Fc fragment of mouse immunoglobulin G inhibits angiogenesis in tumor

Cancer Gene Ther. 2004 May;11(5):363-70. doi: 10.1038/sj.cgt.7700707.

Abstract

Targeting tumor vasculature represents an interesting approach for the treatment of solid tumors. The alpha v beta 3 integrins have been found to be specifically associated with angiogenesis in tumors. By using bacteriophage display technology, Ruoslahti et al found that a group of peptides containing the RGD (Arg-Gly-Asp) motif have high-binding affinity to the alpha v beta 3 integrins in tumors. In this study, we designed a fusion protein containing the RGD sequence and the Fc fragment of mouse IgG in order to target the Fc portion of IgG to the tumor vasculature to elicit an antiangiogenesis immune response. In vivo angiogenesis and tumor studies demonstrated that the fusion protein (RGD/mFc) inhibited tumor angiogenesis and tumor growth and improved overall survival. This approach may generate new therapeutic agents for solid tumor treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Genetic Therapy*
  • Immunoglobulin Fc Fragments / genetics*
  • Immunoglobulin G / genetics*
  • Integrin alphaV / biosynthesis
  • Integrin beta3 / biosynthesis
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / therapy*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / prevention & control*
  • Oligopeptides / genetics*
  • Oligopeptides / metabolism
  • Recombinant Fusion Proteins / genetics*
  • Transduction, Genetic

Substances

  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Integrin alphaV
  • Integrin beta3
  • Oligopeptides
  • Recombinant Fusion Proteins
  • arginyl-glycyl-aspartic acid