Virotherapy for Malignant Gliomas

ASPIRE Award (2019-Present)

Nduka Amankulor, MD (Principal) and Joseph Glorioso, PhD, University of Pittsburgh Medical Center

Malignant gliomas, a class of aggressive brain tumors, are responsible for 10,000 deaths annually in the United States alone. Although all malignant cancers evade the immune system, gliomas are especially effective at masking themselves from immune cells. For example, gliomas often down-regulate or mutate the protein complexes that reveal DNA damage to immune cells. Oncolytic viruses are an attractive therapeutic candidate for gliomas because they can promote an effective immune response in the brain and can be engineered to deliver genetic material to counteract immune-suppressive mutations in the tumor. The Amankulor lab is developing an oncolytic viral therapy for the treatment of malignant gliomas. Along with their collaborators in the laboratory of Dr. Joseph Glorioso at the University of Pittsburgh, they have designed an oncolytic virus that readily infects tumor cells, but not neurons and other nearby healthy cells in the brain. This engineered virus delivers one of several genes that can restore the function of the protein complexes that recruit immune cells to destroy the tumors. The researchers have already shown that infecting glioma cells with the virus in culture leads to the production of these protein complexes. They are now testing this therapy in a mouse model of glioma and investigating which immune cells are recruited to destroy the tumors. These studies will provide essential insight into the efficacy and safety of this oncolytic virus prior to its eventual testing in human patients and potentially lead to a targeted virotherapy for malignant gliomas.