Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients.
OBJECTIVE
Mesothelin is a glycosyl-phosphatidylinositol-anchored glycoprotein present on the cell surface. Mesothelin is a differentiation antigen that is highly expressed on mesothelioma, ovarian cancer, and pancreatic cancer. The existence of a spontaneous humoral immune response to mesothelin in humans has not been fully studied. Here we addressed the issue of whether mesothelin elicits a humoral immune response in patients with mesothelioma and ovarian cancer.


METHODS
Using an ELISA, we analyzed immunoglobulin G antibodies specific for mesothelin in sera from patients with mesothelioma and epithelial ovarian cancer. Tumor specimens were examined by immunohistochemistry for mesothelin protein expression.


RESULTS
Elevated levels of mesothelin-specific antibodies were detected in the sera of 39.1% of patients with mesothelioma (27 of 69 patients) and 41.7% with epithelial ovarian cancer (10 of 24 patients) when compared with a normal control population (44 blood donors; P < 0.01 for both mesothelioma and ovarian cancer). We also found that 53% to 56% of patients with mesothelin immunostaining-positive mesothelioma and ovarian cancer had antibodies specific for mesothelin, whereas only 0% to 8% of patients with negative mesothelin immunostaining had detectable mesothelin-specific antibodies (chi(2) test: P < 0.01 for mesothelioma and P = 0.025 for ovarian cancer).


CONCLUSIONS
Our findings indicate that mesothelin is a new tumor antigen in patients with mesothelioma and ovarian cancer and the immunogenicity of mesothelin is associated with its high expression on the tumor cells. Mesothelin represents an excellent target for immune-based therapies.
Ho
Mitchell
M
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Hassan
Raffit
R
Zhang
Jingli
J
Wang
Qing-Cheng
QC
Onda
Masanori
M
Bera
Tapan
T
Pastan
Ira
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation / Q000276:immunology*; D000951:Antigens, Neoplasm; D001798:Blood Proteins; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D007167:Immunotherapy; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D000090204:Mesothelin; D008654:Mesothelioma / Q000276:immunology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*
D000951:Antigens, Neoplasm; D001798:Blood Proteins; D058851:GPI-Linked Proteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D000090204:Mesothelin