Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients
Sunday, May 15th, 2005.
Clinical Cancer Research. 2005 May 15;11(10):3814-20. [Link]
Ho M, Hassan R, Zhang J, Wang QC, Onda M, Bera T, Pastan I.
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Abstract
Purpose: 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.
Experimental Design: 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.
Glossary
- differentiation
- (dif-er-en-she-A-shun) the normal process through which cells mature so they can carry out the jobs they were meant to do. Cancer cells are poorly differentiated.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- antigen
- (an-tuh-jen) a substance that causes the body's immune system to react. This reaction often involves production of antibodies. For example, the immune system's response to antigens that are part of bacteria and viruses helps people resist infections. Cancer cells have certain antigens that can be found by laboratory tests. They are important in cancer diagnosis and in watching response to treatment. Other cancer cell antigens play a role in immune reactions that may help the body's resistance against cancer.
- tumor
- an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
