Flt3 ligand enhances anti-tumor effects of antibody therapeutics

Int Immunopharmacol. 2012 Mar;12(3):481-6. doi: 10.1016/j.intimp.2011.12.019. Epub 2012 Jan 13.

Abstract

Fms-like tyrosine kinase 3 ligand ([Flt3 ligand], FL) stimulates proliferation and development of a wide range of hematopoietic cells including hematopoietic stem cells and myeloid and lymphoid progenitor cells. FL also has been shown to have anti-tumor effects in a variety of in vivo tumor models. In this study, the effect of FL against tumor growth was investigated in the COLO-205 human colon tumor xenograft model. FL was delivered in vivo by the "hydrodynamics-based gene delivery of naked DNA" method. In this experimental setting, FL and/or the therapeutic antibody anti-carcinoembryonic antigen (CEA) monoclonal antibody was administered. FL alone or anti-CEA antibody alone induced significant growth inhibition; furthermore, FL plus antibody treatment produced synergistic anti-tumor effects. This study is the first demonstration of a synergistic anti-tumor effect between FL and antibody therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neoplasm / therapeutic use*
  • Carcinoembryonic Antigen / biosynthesis
  • Carcinoembryonic Antigen / genetics
  • Cell Line, Tumor
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Drug Synergism
  • Humans
  • Immunity, Cellular / drug effects
  • Immunotherapy*
  • Killer Cells, Natural / drug effects
  • Male
  • Membrane Proteins / blood
  • Membrane Proteins / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy
  • Plasmids / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Neoplasm
  • Carcinoembryonic Antigen
  • DNA, Complementary
  • Membrane Proteins
  • flt3 ligand protein