Inhibition of mesothelin-CA-125 interaction in patients with mesothelioma by the anti-mesothelin monoclonal antibody MORAb-009: Implications for cancer therapy

Lung Cancer. 2010 Jun;68(3):455-9. doi: 10.1016/j.lungcan.2009.07.016. Epub 2009 Sep 9.

Abstract

Background: Mesothelin, a tumor differentiation antigen highly expressed in mesothelioma and ovarian cancer, is the receptor for CA-125 (MUC 16) and this interaction may play a role in tumor metastasis. MORAb-009 is a chimeric anti-mesothelin monoclonal antibody.

Methods: Twenty-four patients with mesothelin expressing cancers were treated on a phase I study of MORAb-009 administered as an intravenous infusion (12.5-400mg/m(2)) weeklyx4 doses with 2 weeks off before the next cycle. This report summarizes the effect of MORAb-009 on serum CA-125 kinetics in the eight patients with mesothelioma who had CA-125 levels measured before and at different time-points following therapy.

Results: MORAb-009 treatment led to a marked increase in serum CA-125 levels in all patients including those without elevated CA-125 levels before therapy. The increase in CA-125 levels was not due to disease progression since CA-125 levels decreased rapidly after stopping MORAb-009 therapy. No patients had signs of peritoneal or pleural inflammation as the possible cause of CA-125 rise. In addition, the elevated CA-125 levels were not due to MORAb-009 interfering with the laboratory assay used to measure CA-125.

Conclusion: The increase in serum CA-125 produced by treatment with MORAb-009 is most likely due to MORAb-009 inhibiting the binding of tumor shed CA-125 to mesothelin present on mesothelial cells lining the pleural and peritoneal cavities. Inhibiting the mesothelin-CA-125 interaction could be a useful strategy to prevent tumor metastasis in mesotheliomas and ovarian cancer.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • CA-125 Antigen / blood
  • Cell Adhesion
  • Disease Progression
  • Female
  • GPI-Linked Proteins
  • Humans
  • Immunotherapy*
  • Male
  • Membrane Glycoproteins / immunology
  • Mesothelioma / blood
  • Mesothelioma / immunology
  • Mesothelioma / metabolism
  • Mesothelioma / pathology
  • Mesothelioma / therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*

Substances

  • Antibodies, Monoclonal
  • CA-125 Antigen
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • mesothelin