Javid Moslehi, MD, director of Cardio-Oncology at Vanderbilt-Ingram Cancer Center, James Allison, PhD, executive director of the Immunotherapy Platform at MD Anderson Cancer Center, Spencer Wei, PhD, a former postdoctoral fellow at MD Anderson, and Justin Balko, PharmD, PhD, associate professor of Medicine and Pathology, Microbiology, and Immunology at VUMC and Vanderbilt-Ingram conceived the research project.
"Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but are associated with immune-related side effects, such as myocarditis, which although infrequent, has up to 50% mortality," said Moslehi, associate professor of Medicine, who is a corresponding author of the study along with Allison. "We have few treatment options for the fulminant cases of ICI-myocarditis."
Immune checkpoint inhibitors target CTLA-4 or PD-1/PD-L1. They are negative regulators which when inhibited, increase activation of the immune system. In few patients, this results in myocarditis or inflammation of the heart muscle.
"As well as identifying a potential treatment, this work gives us a unique opportunity to understand why this syndrome occurs, how to identify patients at risk for it, and maybe even how to prevent it from occurring in the first place" said Balko.
By establishing ICI-myocarditis in the mouse, researchers proved reversing CTLA-4 signaling through abatacept inhibited disease progression and decreased deaths in the mice model. Their work provides mechanistic rationale and support for therapeutic clinical studies.
Moslehi, Joe-Elie Salem, MD, PhD, a former post-doctoral research fellow at Vanderbilt and Johnson, along with researchers from Sorbonne University in Paris, previously reported a patient case in
The New England Journal of Medicine, who recovered from a severe case of immunotherapy-related myocarditis after being treated with abatacept when she did not respond to corticosteroids.
Source: Medindia
