Mesothelin, a protein found on the surface of cells, can be a target for a promising new treatment for mesothelioma, as well as several other cancers, according to a recent study in the journal Molecular Cancer Therapeutics. This protein could also help doctors to diagnose certain cancers.
The reason researcher’s mesothelin has attracted attention as a potential therapeutic target has to do with the way it is distributed in the body. In healthy people, mesothelin is found only in small amounts in the cells lining the lungs, abdominal cavity and heart. However, this protein is produced in excess of mesothelioma, ovarian and pancreatic cancer cells.
To attack these cancers, researchers are looking for expertise in the use of antibodies (a type of immune system protein) that refine the mesothelin while avoiding normal cells. Several research teams and studies using mouse and a combination mouse-human antibody against mesothelin, and the results so far have been promising. However, there is concern that the patient's immune system can recognize animals as antibodies mistakenly attack foreign and them. "This reaction by the immune system is a serious side effect, and makes it risky to re-administer the agent for treating patients," says Yang Feng, PhD, a biologist with the Center for Cancer Research Institute Nanobiology Program National Cancer.
To help prevent this type of immune response, a team of researchers led by Drs. Feng and Dimiter S. Dimitrov investigated using a monoclonal antibody against human-m912-mesothelin. First, the antibody test for the ability to identify mesothelin on epidermoid cancer cells (a type of cancer affecting the lining of the respiratory and digestive tract). Even in low concentrations, m912 could attach to mesothelin in epidermoid cancer cells without binding to healthy cells. The m912 also bound to mesothelin in ovarian cancer cells, although higher concentrations are needed than with squamous cell cancer. The authors say it is because ovarian cells naturally contain small amounts of mesothelin.
For their part, the m912 was not able to kill cancer cells in test tubes. However, with the addition of blood immune cells called peripheral blood mononuclear cells (PBMCs) taken from healthy donors, m912 could mediate the death of cancer cells. It is not toxic to healthy cells. This means m912 can be used as single agent for the treatment of mesothelin positive cancers, said Dr. Feng.
Besides 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 the blood years before being officially diagnosed with mesothelioma. Dr. Feng says mesothelin antibody could be used to detect the protein in the blood of cancer patients, which could help to diagnose disease and determine a patient's prognosis.
Before m912 can be used to diagnose or treat cancer, has to be tested further. "The next logical step is to test in an animal model in the first place," said Dr. Feng. After that, the studies will help determine whether this protein could be a safe and effective treatment of cancer.
The reason researcher’s mesothelin has attracted attention as a potential therapeutic target has to do with the way it is distributed in the body. In healthy people, mesothelin is found only in small amounts in the cells lining the lungs, abdominal cavity and heart. However, this protein is produced in excess of mesothelioma, ovarian and pancreatic cancer cells.
To attack these cancers, researchers are looking for expertise in the use of antibodies (a type of immune system protein) that refine the mesothelin while avoiding normal cells. Several research teams and studies using mouse and a combination mouse-human antibody against mesothelin, and the results so far have been promising. However, there is concern that the patient's immune system can recognize animals as antibodies mistakenly attack foreign and them. "This reaction by the immune system is a serious side effect, and makes it risky to re-administer the agent for treating patients," says Yang Feng, PhD, a biologist with the Center for Cancer Research Institute Nanobiology Program National Cancer.
To help prevent this type of immune response, a team of researchers led by Drs. Feng and Dimiter S. Dimitrov investigated using a monoclonal antibody against human-m912-mesothelin. First, the antibody test for the ability to identify mesothelin on epidermoid cancer cells (a type of cancer affecting the lining of the respiratory and digestive tract). Even in low concentrations, m912 could attach to mesothelin in epidermoid cancer cells without binding to healthy cells. The m912 also bound to mesothelin in ovarian cancer cells, although higher concentrations are needed than with squamous cell cancer. The authors say it is because ovarian cells naturally contain small amounts of mesothelin.
For their part, the m912 was not able to kill cancer cells in test tubes. However, with the addition of blood immune cells called peripheral blood mononuclear cells (PBMCs) taken from healthy donors, m912 could mediate the death of cancer cells. It is not toxic to healthy cells. This means m912 can be used as single agent for the treatment of mesothelin positive cancers, said Dr. Feng.
Besides 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 the blood years before being officially diagnosed with mesothelioma. Dr. Feng says mesothelin antibody could be used to detect the protein in the blood of cancer patients, which could help to diagnose disease and determine a patient's prognosis.
Before m912 can be used to diagnose or treat cancer, has to be tested further. "The next logical step is to test in an animal model in the first place," said Dr. Feng. After that, the studies will help determine whether this protein could be a safe and effective treatment of cancer.
