Promising New Target for Mesothelioma Therapy

Mesothelin, a protein found on the surface of cells, may be a promising new target for treating mesothelioma, as well as several other types of cancers, according to a recent study in the journal, Molecular Cancer Therapeutics. This protein might also help doctors diagnose certain cancers.

The reason why mesothelin has captured researchers’ attention as a potential therapeutic target has to do with the way it is distributed in the body. In healthy people, mesothelin is only found in small amounts in cells lining the lungs, abdominal cavity, and heart. However, this protein is produced in higher amounts by mesothelioma, ovarian, and pancreatic cancer cells.

To attack these cancers, researchers are looking at using specialized antibodies (a type of immune system protein) that hone in on mesothelin while bypassing normal cells. Several research teams are already conducting studies using mouse and combination mouse-human antibodies against mesothelin, and the results so far have been promising. However, there is a concern that patients’ immune systems might recognize animal antibodies as foreign and mistakenly attack them. “This reaction by the immune system is a severe side effect, and makes it risky to re-administer the treatment agent to patients,” explains Yang Feng, PhD, a biologist with the Center for Cancer Research Nanobiology Program of the National Cancer Institute.

To help prevent this type of immune response, a team of researchers led by Drs. Feng and Dimiter S. Dimitrov investigated the use of a human monoclonal antibody—m912—against mesothelin. They first tested the antibody’s ability to recognize mesothelin on cells taken from epidermoid cancer (a type of cancer that affects the lining of the respiratory and digestive tracts). Even at low concentrations, m912 was able to attach to mesothelin on the epidermoid cancer cells, without binding to healthy cells. The m912 also bound to mesothelin on ovarian cancer cells, although higher concentrations were needed than with the epidermoid cancer cells. The authors say this is because ovarian cells naturally contain smaller amounts of mesothelin.

On its own, m912 was not able to kill cancer cells in test tubes. However, with the addition of immune blood cells called peripheral blood mononuclear cells (PBMCs) taken from healthy donors, m912 was able to mediate the killing of cancer cells. It was not toxic to healthy cells. This means m912 can potentially be used as a single agent for treating mesothelin-positive cancers, Dr. Feng says.

In addition to its potential use in cancer treatment, mesothelin is also being investigated as a diagnostic marker. Workers who have been exposed to asbestos (a major risk factor for mesothelioma) show high levels of mesothelin in their blood years before they are formally diagnosed with mesothelioma. Dr. Feng says antibodies to mesothelin could be used to detect the protein in the blood of cancer patients, which could help both diagnose the disease and determine a patient’s prognosis.

Before m912 can be used to diagnose or treat cancer, it needs to be tested further. “The next logical step is to test it in an animal model first,” according to Dr. Feng. After that, human studies will help determine whether this protein might prove to be a safe and effective cancer treatment.

Editor’s Note:
Many patients have heard about Mesomark  The Mesomark assay is a blood test, using an Enzyme-Linked Immunosorbent Assay (ELISA) format, for the quantitative measurement of Soluble Mesothelin-Related Peptides (SMRP) in human serum.

Source:

Feng Y, Xiao X, Zhu Z, Streaker E, Ho M, Pastan I, Dimitrov DS. A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependant cell-mediated cytotoxicity. Mol Cancer Ther. 2009;8:1113-1118.