The cell-surface glycoprotein mesothelin is poised to be a key part of several new immunotherapy approaches for the treatment of malignant pleural mesothelioma, a treatment-resistant cancer caused by asbestos.
A team of top mesothelioma researchers with the National Cancer Institute’s Center for Cancer Research recently published their analysis of several ongoing studies of therapies that target mesothelin in mesothelioma treatment.
Mesothelin’s Relationship to Mesothelioma
Mesothelin is a protein that is highly expressed in several malignancies, including ovarian cancer, pancreatic cancer, malignant mesothelioma and some lung cancers.
Mesothelin is especially valuable as a target for mesothelioma treatment because it is primarily expressed by mesothelial cells which make up the membranes where mesothelioma tumors start. These cells, as the authors of the new study point out, are “expendable”, meaning that their destruction with targeted drugs would not threaten vital organs.
Mesothelin is also considered the gold standard biomarker for diagnosing malignant mesothelioma.
Mesothelin as a Target for Immunotherapy
In a new report in the Journal of Clinical Oncology, mesothelioma researcher Raffit Hassan, MD, and colleagues offer an overview of mesothelin-focused therapies currently in development for the treatment of mesothelioma.
One category of mesothelin-based therapies mentioned is immunotoxins that target cells expressing mesothelin. These include experimental drugs such as SS1P, and RG7787/LMB-100. Preliminary studies of SS1P produced “significant antitumor activity” in pleural mesothelioma, according to Dr. Hassan.
Another category is antibodies like the monoclonal anti-mesothelin antibody amatuximab (MORAb-009). The international ARTEMIS trial of amatuximab has indicated that it may boost the effectiveness of standard chemotherapy. Amatuximab is currently being tested as a potential first-line mesothelioma therapy. A similar agent, anetumab ravtansine, is the focus of a multi-center trial as a second-line therapy.
Other mesothelin-focused therapies mentioned in the report include a drug made from a live bacteria and vaccines that can induce T-cell immune response to mesothelin.
The bacteria-based drug, called CRS-207, unmasks mesothelioma cells to make them vulnerable to immune system attack. A recent human trial of CRS-207 along with standard mesothelioma chemotherapy produced an unprecedented 90 percent disease control rate and prompted researchers to refer to it as “an exciting agent for patients with mesothelioma.”
“There has been substantial progress in the development of different approaches to target mesothelin for cancer therapy,” concludes Dr. Hassan.“These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer.”
Hassan, R, et al, “Mesothelin Immunotherapy for Cancer: Ready for Prime Time?”, December 2016, Journal of Clinical Oncology