Mesothelin: a new target for immunotherapy

Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3937-42. doi: 10.1158/1078-0432.CCR-03-0801.

Abstract

Mesothelin is a differentiation antigen present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The mesothelin gene encodes a precursor protein that is processed to yield the 40-kDa protein, mesothelin, attached to the cell membrane by a glycosylphosphatidyl inositol linkage and a 31-kDa shed fragment named megakaryocyte-potentiating factor. The biological function of mesothelin is not known. Mesothelin is a promising candidate for tumor-specific therapy, given its limited expression in normal tissues and high expression in several cancers. SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin that is undergoing clinical evaluation in patients with mesothelin-expressing tumors. There is evidence that mesothelin is an immunogenic protein and could be exploited as a therapeutic cancer vaccine. A soluble mesothelin variant has been identified and could be a useful tumor marker for malignant mesotheliomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Clinical Trials as Topic
  • GPI-Linked Proteins
  • Glycosylphosphatidylinositols / chemistry
  • Humans
  • Immunohistochemistry
  • Immunotherapy / methods*
  • Immunotoxins / chemistry
  • Megakaryocytes / chemistry
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Nude
  • Models, Chemical
  • Neoplasms / metabolism
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • Glycosylphosphatidylinositols
  • Immunotoxins
  • Membrane Glycoproteins
  • Recombinant Proteins
  • mesothelin