When you received your mesothelioma diagnosis, your doctor probably told you the type of cell that makes up the mesothelioma growing inside you — epithelioid, biphasic or sarcomatoid.
If your mesothelioma cell type is epithelioid, your doctor may be able to soon offer you a promising new treatment option. It’s a drug already approved by the U.S. Food and Drug Administration, although not for the treatment of mesothelioma.
The drug is called brentuximab vedotin and researchers from Case Western Reserve University School of Medicine recently discovered that it may be beneficial for epithelioid mesothelioma patients.
Brentuximab vedotin is mainly used to treat victims of Hodgkin’s disease, which has something in common with mesothelioma — an antigen called CD30. CD30 is a cytokine receptor that belongs to tumor necrosis factor superfamily 8.
CD30 is bad because its stops apoptosis. Apoptosis is the process by which damaged or otherwise abnormal cells kill themselves in order to save the host body.
The Case Western researchers, in Molecular Cancer Therapeutics, describe brentuximab vedotin as having “remarkable success” in preventing CD30 from interfering with apoptosis.
How the Drug Attacks Mesothelioma
Formally speaking, brentuximab vedotin is known as an antibody-drug conjugate. An antibody-drug conjugate is what you get when you take a monoclonal antibody and pair it with a cytotoxic agent.
The monoclonal antibody used in brentuximab vedotin is engineered to burrow into a target cell after first binding to a specified cell-surface receptor, in this case CD30.
The cancer cell’s own enzymes then perform an act of betrayal by causing the cytotoxic agent to be released from the monoclonal antibody. Once freed, the cytotoxic agent then proceeds to kill the cell.
In brentuximab vedotin, the cytotoxic agent is monomethyl auristatin E. It attaches to the monoclonal antibody with the help of a protease-cleavable linker.
The linker only allows release of the cytotoxic agent when the cancer cell’s enzymes step forward and start grabbing at it.
This little feature is important to the drug’s success because hanging onto the cytotoxic agent until the cancer cell’s enzymes demand it ensures maximum delivery of the deadly ingredient.
And since the CD30 receptor usually only exists on cancer, there is little likelihood of a healthy cell receiving the cytotoxic agent.
Four Mesothelioma Cell Lines Studied
Scientists know a lot about CD30 because they’ve studied it for quite some time with regard to Hodgkin’s disease and anaplastic large-cell lymphoma.
The Case Western researchers said they decided to test brentuximab vedotin on mesothelioma after taking note of earlier findings that non-lymphoid tumors — such as mesothelioma — had CD30 antigens.
“Given the remarkable success of brentuximab vedotin in lymphoid malignancies, we undertook a study to examine the incidence of CD30 in mesothelioma and to investigate the ability to target CD30 antigen in mesothelioma,” the researchers wrote.
The researchers obtained specimens from four mesothelioma cell lines and examined them in detail by means of immunohistochemistry. The cell lines they looked at were H28, H2052, H2452 and 211H.
As hypothesized, they found CD30 expression in many of the mesothelioma specimens. Overall, CD30 expression was by far most common in the epithelial type of mesothelioma.
The researchers then treated the mesotheliomas with brentuximab vedotin. All of the mesotheliomas were contained in lab dishes, not human bodies.
Being in dishes, the researchers could easily see the drug at work. They reported that brentuximab vedotin caused the mesothelioma cells to stop growing and weaken.
The company Seattle Genetics, which produces brentuximab vedotin under the brand name Adcetris, is conducting four Phase 3 clinical trials in other types of CD30-positive malignancies beyond those for which the drug’s use is currently approved.