Combination Immunotherapy Treatment Looks Promising for Mesothelioma

Illustration of mesothelioma research

Researchers at the Vaccine and Immunotherapy Center (VIC) at Massachusetts General Hospital discovered a novel immunotherapy combination treatment that shows promise for mesothelioma. While the Phase I clinical trial was only applied to mouse models so far, researchers were impressed with the initial results, which more than doubled overall survival time, and they hope to expand clinical development soon.

The new treatment is a combination of immune modulator AMD3100 (plerixafor) with an experimental drug, VIC-008 or Jantibody. VIC-008 is described as a fusion protein that combines an immune-activating protein from tuberculosis bacteria with an antibody targeting mesothelin, a protein present in mesothelioma tumors. Since mesothelin has also been found in ovarian and pancreatic cancer, researchers are also working to test the efficacy of this new treatment for these other cancers.

Immune modulators have a different mechanism of action than immune checkpoint inhibitors like pembrolizumab (Keytruda®), ipilimumab (Yervoy®), and other cancer immunotherapy drugs. Certain proteins released by tumor cells act as “checkpoints” to slow down immune cell response rate; checkpoint inhibitors block those checkpoints, thus facilitating an anti-tumor immune response. Rather than acting as a checkpoint blockade, immune modulators stimulate the immune system to boost its ability to facilitate cancer cell death.

Through their studies, cancer center researchers discovered the combination of these novel treatments significantly reduced tumor size and increased overall survival compared to either drug being applied individually. In prior cancer research, scientists have seen AMD3100’s ability to suppress metastasis and tumor growth in advanced melanoma by enacting some control over the body’s T cells, an important aspect of immune system response.

When researchers considered the elevated levels of certain proteins in the body as mesothelioma becomes more advanced, they believed VIC-008 and AMD3100 could provide an effective combination therapy to control tumor growth.

Jeffrey Gelfand, a VIC investigator who developed VIC-008 as a treatment for ovarian cancer in honor of his wife, who unfortunately passed away from the disease, explained how the agents work together. “AMD3100 is already an FDA-approved drug, whose use and application the MGH VIC is hoping to extend in various cancers. Jantibody focuses the AMD3100-invigorated immune response on critical tumor structures, markedly enhancing tumor control. We hope these data will help to move Jantibody closer to human tumor therapy, fulfilling one of my wife’s last wishes.”

One of the other lead scientists on the study, Huabiao Chen, further explained how the combination treatment could work. “We believe that we can find an approach that combines Jantibody and AMD3100 to regroup and redirect immune responses in order to combat cancer.”

With such promising results from the preclinical studies, these researchers hope to continue the research with groups of mesothelioma patients, as well as patients suffering from ovarian or pancreatic cancer. With further study, they hope to determine the most effective combination approaches to cancer treatment and continue to help research get closer to finding a cure.