Mesothelin: a new target for immunotherapy.
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.
Hassan
Raffit
R
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland, USA. hassanr@mail.nih.gov
Bera
Tapan
T
Pastan
Ira
I
D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002986:Clinical Trials as Topic; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D000922:Immunotoxins / Q000737:chemistry; D008533:Megakaryocytes / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D000090204:Mesothelin; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009369:Neoplasms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D000922:Immunotoxins; C000715527:MSLN protein, human; D008562:Membrane Glycoproteins; C000715528:Msln protein, mouse; D011994:Recombinant Proteins; D000090204:Mesothelin