Mesothelin targeted cancer immunotherapy.
Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. It is, however, highly expressed in several human cancers including malignant mesothelioma, pancreatic, ovarian and lung adenocarcinoma. The normal biologic function of mesothelin is unknown but recent studies have shown that it binds to CA-125 and may play a role in the peritoneal spread of ovarian cancer. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. Three mesothelin targeted agents are in various stages of clinical evaluation in patients. These include SS1P (CAT-5001) a recombinant immunotoxin targeting mesothelin, MORAb-009 a chimeric anti-mesothelin monoclonal antibody and CRS-207 a live-attenuated Listeria monocytogenes vector encoding human mesothelin. These ongoing clinical trials will help define the utility of mesothelin as a target for cancer therapy.
Hassan
Raffit
R
Solid Tumor Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4264, USA. hassanr@mail.nih.gov
Ho
Mitchell
M
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines; D058851:GPI-Linked Proteins; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008089:Listeria monocytogenes; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000090204:Mesothelin; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C474515:SS1(dsFv)PE38; C526187:amatuximab; D000090204:Mesothelin