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Mass General Researchers Discover Drug Combination That Targets Mesothelin

Researchers at the Vaccine and Immunotherapy Center (VIC) at Massachusetts General Hospital (MGH, Mass General) have discovered that a combined treatment with two cancer immunotherapy drugs is effective at prolonging survival in mouse models of the aggressive cancer mesothelioma. The two drugs, known as AMD3100 (plerixafor) and VIC-008, more than doubled the animals’ survival time.

AMD3100 was previously approved for the stimulation of stem cell production prior to bone marrow transplantation, and the teams’ investigational drug VIC-008 (also known as Jantibody), is a fusion protein combining an immune-activating protein from the tuberculosis bacteria with a small antibody fragment targeting mesothelin, a protein expressed in several types of tumors – including mesothelioma, pancreatic, and ovarian cancer.

In a recent MGH News Release, Senior Author of the study and Director of the MGH-VIC Mark Poznansky said, “Mesothelioma, a tumor that is caused by asbestos exposure, has been extremely hard to treat; and patients usually survive only 12 to 18 month after diagnosis. Since the advent of cancer immunotherapy, people have tried to apply immunotherapeutic drugs to mesothelioma with limited success. We are very excited at the prospect that this drug combination may be much more effective in prolonging patients’ lives.”

According to the team, among the mechanisms identified as underlying the combination treatment’s effects was changing a population of immunosuppressive T cells into a type that could enhance an antitumor immune response. “The apparent ability to change immunosuppressive T cells within the tumor into T cell types that are more active and potentially helpful against cancer was a really exciting finding, and one that we’re continuing to investigate,” said Poznansky.

Lead scientist for the study Huabiao Chen added, “We believe that we can find an approach that combines Jantibody and AMD3100 to regroup and redirect immune responses in order to combat cancer.” Jeffrey Gelfand, who collaborated with Poznansky on the study, is an MGH-VIC investigator who developed Jantibody – named in memory of his wife Janet who succumbed to ovarian cancer – as a potential treatment for ovarian cancer

Gelfand notes that, “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,” he said, “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.”

If you have been diagnosed with mesothelioma, talk to your doctor about innovative combination treatments such as AMD3100 and VIC-008. Investigational treatments such as this could be effective at helping treat your specific type of mesothelioma.

 

Sources

Poznansky, Mark. "Combination Immunotherapy Improves Survival in Mouse Models of Mesothelioma." Massgeneral.org. Massachusetts General Hospital (MGH), 02 Apr. 2018. Web. 16 Apr. 2018.