An immunotherapy vaccine by itself won’t stop malignant pleural mesothelioma, but its ability to enhance the effectiveness of cytoreductive surgery could become the treatment breakthrough
that doctors and patients have been seeking for years.
The combination of immunotherapy and surgery, which proved especially effective in preclinical research at the University of Pennsylvania, should add to the multimodal treatment approach that includes chemotherapy and radiation for mesothelioma patients.
“It is very promising,” renowned thoracic surgeon and mesothelioma specialist Dr. Sunil Singhal, of the Abramson Cancer Center, told Asbestos.com. “It’s way too early to be sure, but this could become a really big deal.”
Singhal, who also serves as director of the Thoracic Surgery Research Laboratory at Penn Medicine, believes reducing the mesothelioma tumor burden with surgery gives the immunotherapy vaccine a much better chance of success.
“What we’ve seen so far is that the vaccine by itself, with advanced disease, doesn’t seem to work very well,” Singhal said. “But if the vaccine can rev up or amplify the immune system, and we take out the tumors, it can attack what’s left over and finish the job. There is real potential here.”
Difficulty Developing the Vaccines
Although preclinical research continues to support the development of an immunotherapy approach or helping a patient’s own immune system to attack the cancer, effective vaccines have been difficult to develop.
Once tumors are advanced and well established, they develop an immunosuppression ability that even the most powerful drugs can’t break. The vaccines are much more effective when delivered in the early stages of cancer.
The laboratory research at UPenn Medicine was detailed last month in Immunology Letters. The conclusion reached: Debulking the tumor can restore the efficacy of vaccine-based immunotherapy. It could become an attractive therapeutic option for mesothelioma patients.
“I’ve always believed that with mesothelioma, you can’t get away with just surgery, or just chemotherapy, or just radiation,” Singhal said. “The best way to handle it is a combination that may eventually include another step.”
Building Momentum with CRS-207
The vaccine used in the laboratory research, and now part of a multicenter clinical trial, was the modified version of Listeria (CRS-207) that has become a popular topic with oncologists around the country.
The genetically modified Listeria virus earlier this year was granted orphan drug designation for mesothelioma by the U.S. Food and Drug Administration (FDA). The designation promotes the research and development of new drugs, especially for rare diseases such as mesothelioma.
The FDA already has approved effective immunotherapy vaccines for more common cancers such as those of the breast, prostate, skin and lungs. But the agency hasn’t approved any for mesothelioma.
Cancer vaccines in the past have produced notable responses in laboratory animals for a variety of malignancies but have not translated well in human trials. CRS-207 is one of the first that has shown particular promise in clinical trials for mesothelioma.
The CRS-207 vaccine produced a 94 percent rate of disease control, either partial response or stable disease, in a recent trial involving patients who were not candidates for surgery.
There has been no clinical trial yet that combines the CRS-207 vaccine with cytoreductive surgery, but the first may not be far away.
“We’re making progress with this very tough disease,” Singhal said. “We’re finally getting some momentum going.”