Over 20 years ago, researchers at the National Cancer Institute (NCI) discovered the antigen, mesothelin. To this day, it has been an attractive target for investigative studies due to its overexpression in mesothelioma tumors. Dr. Raffit Hassan, head of Thoracic and Solid Tumor Immunotherapy Section at the NCI, is now trying to combine a mesothelin-targeted drug with immunotherapy for mesothelioma to help combat pleural and peritoneal mesothelioma.
What is Mesothelin?
Mesothelin is a protein found on the surface of mesothelial cells lining the pleura, peritoneum, and pericardium. It is often highly expressed in many cancers, including epithelioid mesothelioma. Since this protein lays on extraneous tissue, the risk of increased toxicity in a patient’s body is significantly reduced. This makes it an ideal target for experimental drugs.
Dr. Hassan explained in an interview how the development of these immunotherapy drugs could drastically improve the treatment of mesothelioma. This is achieved specifically through being able to conduct clinical trials on patients with minimal harm to healthy organs in their bodies:
“The most important thing in terms of targeted therapy is the expression of mesothelin. It is really hard to find tumor antigens that can be targeted, but the fact that it is not expressed on an important organ makes it a good target for antibody-based therapies.”
Combining LMB-100 with Pembrolizumab
LMB-100 is a man-made immunotoxin that targets mesothelin. After it binds to mesothelin on tumors, it attacks and destroys cancer cells. Pembrolizumab, or Keytruda, is a monoclonal antibody that fights against PD-1. It blocks the PD-1 pathway to prevent cancer cells from hiding and ultimately helps the immune system identify and combat cancer cells without having to introduce toxic substances to the body to fight cancer like chemotherapy and radiation.
LMB-100 is currently being used in clinical trials to find a tolerable dose. It has shown activity in testing it on mesothelioma cancer cells in the lab. Pembrolizumab has been used in previous trials resulting in a 76% response rate. Researchers are hoping that in combining the two drugs, it will be an effective treatment for refractory mesothelioma.
In 2017, Dr. Hassan discussed the mesothelin antigen and how it can improve immunotherapy for mesothelioma:
What to Expect in this Immunotherapy Trial
The National Cancer Institute Center for Cancer Research in Bethesda, Maryland will soon start recruiting for this immunotherapy trial combining the immunotoxin LMB-100 with Pembrolizumab for pleural and peritoneal mesothelioma. Patients will receive LMB-100 via IV on days 1, 3 and 5 of a 21-day cycle. After two cycles are completed, patients will receive Pembrolizumab via IV on day 1 of each 21-day cycle. Scans will be taken every 6 weeks.
Patient Inclusion Criteria:
- Epithelioid or biphasic cell type
- Not a surgical candidate
- At least 1 prior administration of Alimta and Cisplatin
For more information about this clinical trial and the National Cancer Institute, please contact the Mesothelioma Guide. Our registered nurse advocate, Karen Ritter, is available to answer your questions. You can reach her at 888-385-2024, ext. 102 or by emailing karen@mesotheliomaguide.com.
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