UNC Cancer Care Director H. Shelton Earp, MD, has received a five-year, $1.74 million grant from the National Institutes of Health to study a potential new strategy for improving immunotherapy drug responses in patients with melanoma.
Earp and his colleagues will study whether the MERTK protein suppresses the immune system’s response to cancer. The researchers believe this protein signal could be preventing some melanomas from having a more robust response to “checkpoint inhibitors” drugs, which are widely used in cancer patients. The researchers will study whether investigational compounds developed at UNC can reverse the MERTK protein’s immunosuppressive effect.
“There is great interest in the potential for harnessing the immune system to fight cancer,” said Earp, who is a UNC Lineberger member and the Lineberger Professor of Cancer Research at the UNC School of Medicine. “We know that checkpoint inhibitors work for fewer than half of melanoma patients. But what about the rest - the patients who don’t appear to have an effective immune response? These are the patients we want to help.”
Checkpoint inhibitors work by unleashing the brakes in specialized tumor-killing cells called T-cells. Earp’s group, which discovered the gene that codes for the MERTK protein, will test whether it is possible to inhibit the immuno-suppressive MERTK protein signal in order to enhance the tumor-killing activity of T-cells when combined with checkpoint inhibitors.
Earp and his colleagues will study the role that MERTK and other signals play in the body’s immune response to melanoma. Additionally, they will assess whether compounds developed at UNC can suppress MERTK and other proteins to produce a stronger cancer response from the immune system in laboratory models of melanoma. A Melanoma Research Alliance team science award helped to initiate the project.
The UNC-developed compounds, including MRX-2843, were developed in the UNC Center for Integrative Chemical Biology and Drug Discovery, led by UNC Lineberger’s Stephen Frye, PhD, the Fred Eshelman Distinguished Professor in the UNC Eshelman School of Pharmacy. A previous grant awarded to Earp and Frye from the National Cancer Institute’s Experimental Therapeutics program funded the development funded the chemical development of MERTK inhibitors.
“The new grant from the National Cancer Institute will allow us to study both the basic aspects of how tumors suppress the immune system as well as to set the stage for a new therapeutic approach in the rapidly expanding area of immunotherapy of cancer,” Earp said.
Frye, Earp and others are co-founders of the startup company Meryx Inc. that was launched to allow the clinical development of compounds that inhibit MERTK activity for patients with cancer. Meryx has licensed the rights to MERTK inhibitors from UNC. The company received start-up funding through Carolina KickStart, the university program that helps UNC start-ups companies with technology validation, product and business development.