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Ambassadors philanthropic funding key to discovery

May 30, 2017 | Leigh MacMillan

Before they became collaborators, they were competitors.

On a Saturday in November 2015, Javid Moslehi, M.D., and Justin Balko, Pharm.D., Ph.D., met for the first time.

They were competing for Discovery Grants funded by the Vanderbilt-Ingram Cancer Center (VICC) Ambassadors, a group of young professionals who support groundbreaking cancer research. VICC Ambassadors provide “seed funding” to support early-stage, high-risk research.

Each faculty member gave a 10-minute presentation, followed by time for questions.

Moslehi, assistant professor of Medicine and director of the Cardio-Oncology Program, proposed using a cellular screening platform to assess the cardiotoxicity of novel cancer therapies. Balko, assistant professor of Medicine and Cancer Biology, described using non-invasive imaging to monitor lymphocytes (T cells) in tumors as a biomarker for response to immunotherapies.

Moslehi and Balko were both awarded Discovery Grants, and realized in further conversations at a celebratory event that there might be future opportunities for collaboration.

That partnership came sooner than they imagined. Two patients with metastatic melanoma who received a combination of immunotherapy drugs at Vanderbilt developed acute inflammation of the heart (myocarditis) after their first doses of the drugs, and despite aggressive treatment, they died.

Moslehi, Balko, and a large group of investigators including Douglas Johnson, M.D., MSCI, assistant professor of Medicine and clinical director of the Melanoma Program, collaborated to study the cases.

They analyzed clinical records and used tissue samples to identify the cell types present in heart muscle, skeletal muscle and tumors. They also queried Bristol-Myers Squibb corporate safety databases to assess the frequency of myocarditis in a larger population of patients treated with the immunotherapy drugs.

The group’s Nov. 3 , 2016, report in The New England Journal of Medicine detailed the rare, and potentially fatal, drug reaction. The following appears at the end of the scientific summary: Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.

“There were 32 authors and everybody had grants, there were probably 50 grants or so. We had to list the single most important grant with the summary, and we decided it was the VICC Ambassadors grant I received,” Moslehi says.

Because the Ambassadors funding was flexible, Moslehi was able to use it to move quickly in studying the patient deaths, he says.

“I didn’t expect to be working in this area, and as a junior faculty member with limited resources, this money was really critical.”

These studies and others have revealed a similarity between the myocarditis reaction and heart transplant rejection, suggesting that therapies used to suppress the immune response following transplant may be useful. Moslehi and others are now using the drug anti-thymocyte globulin (ATG), which is used to prevent transplant rejection, to treat severe reactions to immunotherapies.