Anti-ABCG2 monoclonal antibody in combination with paclitaxel nanoparticles against cancer stem-like cell activity in multiple myeloma

Nanomedicine (Lond). 2014 Jan;9(1):45-60. doi: 10.2217/nnm.12.216. Epub 2013 Mar 27.

Abstract

Aim: To investigate the effects of anti-ABCG2 monoclonal antibodies (mAbs) in combination with paclitaxel iron oxide nanoparticles (PTX-NPs) on CD138(-)CD34(-) multiple myeloma (MM) cancer stem cells (CSCs) in JJN3 cells.

Materials & methods: PTX-NPs were prepared using the hydrophobic interaction of the polyoxypropylene chain and oleic acid on the surface of iron oxide NPs and were targeted to the ABCG2 transporter overexpressing MM CSCs with mAbs.

Results: The data showed that MM CSCs have strong drug resistance and tumorigenicity compared with non-MM CSCs. PTX-NPs combined with mAbs led to a significant reduction in the tumor volume, a visible alleviation of lytic bone lesions and a markedly increased survival rate in contrast to using a single agent in MM CSCs when it was transplanted to nonobese diabetic/severe combined immunodeficiency mice.

Conclusion: This study is the first to report on the anti-MM CSC activity by PTX-NPs as a single agent or used together with anti-ABCG2 mAbs to treat MM. These findings provide a rationale for future clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / immunology*
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Ferric Compounds / chemistry
  • Mice
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Neoplasm Proteins / immunology*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / immunology
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antibodies, Monoclonal
  • Drug Carriers
  • Ferric Compounds
  • Neoplasm Proteins
  • ferric oxide
  • Paclitaxel