Monitoring Mesothelin Levels in Those Exposed to Asbestos Could Lead to Earlier Diagnosis of Mesothelioma

Cancer Researchers have long been searching for indicators that could hold the key to diagnosing mesothelioma at an early stage. Mesothelioma has a long latency period with initial asbestos exposures which occurred 20 to sometimes 50 years before the cancer develops. Typically, diagnoses occurs when the disease is late stage and therefore patients are presented with a poor prognosis.

In 2007, researchers out of Tokyo began a long term and large scale screening of construction workers and plumbers with a risk of asbestos exposure to determine whether the protein mesothelin (N-ERC/MSLN) could be used as an early detection method. N-ERC/MSLN is a protein present on normal mesothelial cells which line the internal organs and are present throughout the entire body, in mesothelioma and in some other forms of cancer, N-ERC/MSLN is over expressed.

The researchers screened 40,000 potential participants through a construction workers union and a national health insurance association who had a high risk of exposure to asbestos as a result of their occupations in construction and plumbing. Of the 40,000 participants, 62 were identified as being high risk for the development of mesothelioma due to elevated levels of N-ERC/MSLN in their blood.

The participants underwent annual blood tests to monitor N-ERC/MSLN levels. Out of the 62 participants, two have subsequently developed mesothelioma. The remaining participants will continue to be monitored with yearly blood tests.

Early detection can lead to earlier diagnosis of mesothelioma which could allow for earlier treatment. This in turn offers the potential for prolonged survival and better quality of life due to less invasive disease management.  Source

Massachusetts General Hospital Develops Potential Vaccine for Mesothelioma and Ovarian Cancers

In the hopes of creating a potential vaccine for mesothelioma and ovarian cancer, researchers at Massachusetts General Hospital (MGH) have engineered a protein which has shown prolonged survival in animal models with both types of cancer.

Researchers combined a protein programmed to target an antibody fragment that targets mesothelin, with a protein from tuberculosis bacteria that stimulates the activity of dendritic, or immune cells. The researchers activated the dendritic cells to target tumor cells while remaining inside the patient's body. Typically approaches to developing cancer vaccines using these types of immune cells require extracting cells from the patient’s body, treating them with the vaccination agent, and returning them into the body.

"Many patients with advanced cancers don't have enough functioning immune cells to be harvested to make a vaccine, but our protein can be made in unlimited amounts to work with the immune cells patients do have," explains study co-author Jeffrey Gelfand, MD, senior scientist at the MGH Vaccine and Immunotherapy Center. "We have created a potentially much less expensive approach to making a therapeutic cancer vaccine that, while targeting a single tumor antigen, generates an immune response against multiple antigens.”

The mesothelin-targeting protein binds to mesothelin cells, activates the dendritic cells, and enhances the cells' processing and presentation of several different tumor antigens, inducing a number of T-cell-based immune responses. Treatment with the protein significantly slowed tumor growth and extended survival in mouse models of both tumors.

Mesothelioma, ovarian cancer, and pancreatic cancer all have the potential to be treated with a mesothelin targeting vaccine. "Immunotherapy is generally nontoxic, so this vaccine has the potential of safely extending survival and reducing the effects of these tumors, possibly even cutting the risk of recurrence.”

The MGH team just received a two-year grant from the Department of Defense Congressionally Directed Medical Research Program to continue their research.  Source