Clapper, Patti, Schweizer and Mason

Mesothelioma is a rare malignancy that can occur in the lining of the lungs (pleura), heart (pericardia), or abdomen (peritonea).  All forms of mesothelioma commonly are resistant to standard treatments and have poor prognosis of less than a year survival time in most cases.  Due to this, clinical trials continue to search for safe and effective therapeutic interventions that may slow progression and perhaps lead to discovery of a cure for mesothelioma.

Immunotherapy is one avenue being explored through clinical trials as one way to manage and treat mesothelioma.  This method uses an agent to trigger, induce or enhance the body’s natural immune response system in defense against tumors.  Immuno cell therapy combined with other standard forms can destroy tumor cells, thereby slowing progression of the cancer and prolonging survival times.

Data from previous clinical trials have shown that adenoviral vector expressing interferon-beta (Ad.IFN-beta), when administered into the pleural cavity, has resulted in gene transfer and led to antitumor immune responses for patients diagnosed with mesothelioma.  A recent study researched whether giving two doses versus one would be safe and more effective at inducing an immune response and stabilizing the cancer. 

The phase I trial involved ten patients diagnosed with malignant pleural mesothelioma, each given two doses of IFN-beta within a period of seven days or longer.  Interferon-beta is a protein made and released by white blood cells as an immune response to tumor cells.  IFN’s cause cells to communicate, activate immune cells, and can trigger a response that interrupts tumor cell replication.

Interferon therapy is usually used in combination with chemotherapy and radiation as a treatment for mesothelioma, with some evidence of successful effect.   For pleural mesothelioma, IFNs are administered through a catheter into the pleura.  Most common side effects are general flu-like symptoms, such as fatigue, nausea, temperature, dizziness and muscle pain.    Pharmaceutical forms of interferon betas can come in liquid, lyophilized or biogeneric forms. 

Data from this clinical trial showed that multiple doses were well tolerated; however the gene transfer process was blocked by preexisting anti-AAV neutralizing antibodies (NABs).   AAV stands for adeno-associated virus vectors, which have become main vehicles in gene therapy.  Anti-AAV antibodies are naturally acquired by human infections, and can be used as part of cancer therapy by way of gene transfer.

Further clinical research is supported to verify the antitumor efficacy of this agent in controlling and/or eradicating mesothelioma tumors.