An exciting new research development may help make immunotherapy vaccines effective for more mesothelioma patients, including those with advanced disease who have not been able to benefit from these treatments.
Immunotherapy works by harnessing the power of the body’s own immune system and directing it to attack cancer cells. Unfortunately, as mesothelioma tumors grow, they release increasing amounts of an immune system suppressor designed to ward off an attack. The bigger the tumor, the more powerful the immune suppression and the less effective immunotherapy drugs are likely to be.
At the same time, larger mesothelioma tumors may also produce less mesothelin, a protein that can be used to help immunotherapy vaccines target cancer cells. With less mesothelin and strong immunosuppression, advanced mesothelioma can be almost invisible to even the most powerful immunotherapy vaccines.
But researchers at the University of Pennsylvania say they may have found a way around the problem. Using mice inoculated with mesothelioma cells, they discovered that a bacteria-based immunotherapy vaccine that was not working on large tumors became effective again after cytoreductive surgery reduced the size of tumors.
“Surgical cytoreduction of established tumors restored the antitumor potency of the therapeutic vaccine, with significantly reduced tumor burden at post-operative day 18,” reports University of Pennsylvania researcher Gregory Kennedy.
The team found that surgery reduced the immunosuppressive power of the remaining mesothelioma cells to levels nearly equal to mice that had never had cancer. With less ability to guard against an immune system attack, these mesothelioma cells were once-again susceptible to the Listeria monocytogenes-based vaccine.
Earlier this year, the FDA granted orphan drug status to the mesothelioma vaccine used in this experiment, a drug made from an attenuated (less potent) version of the bacteria Listeria monocytogenes called CRS-207.
Kennedy, GT, “Surgical cytoreduction restores the antitumor efficacy of a Listeria monocytogenes vaccine in malignant pleural mesothelioma”, May 18, 2015, Immunology Letters, Epub ahead of print