In This Section

Metabolic Reprogramming Using Oncolytic Viruses to Improve Immunotherapy

Metabolic Reprogramming Using Oncolytic Viruses to Improve Immunotherapy


Greg M. Delgoffe, PhD
Assistant Professor, Department of Immunology
University of Pittsburgh
Pittsburgh, Pennsylvania


The last several years have brought considerable progress to the field of immunotherapy, the goal of which is to stimulate and amplify a patient’s own immune response to recognize and destroy tumor cells. Despite the remarkable success of immunotherapy in some forms of cancer, many tumors do not respond because the cancer cells change their surrounding environment, termed the tumor microenvironment, so that it is restrictive to immune cell function. For example, tumor cells use molecules called immune “checkpoints” to suppress anticancer immune function. In addition, tumor cells need a lot of fuel to continue to grow, evolve and metastasize, and in so doing, effectively starve the microenvironment and incoming immune cells of the energy they need to carry out their anti-tumor functions. This proposal will focus on two immunotherapy approaches that have proven successful: 1) viruses that specifically infect and destroy tumor cells (oncolytic viruses), and 2) drugs that inhibit immune checkpoints thereby releasing the inhibition on immune cell function. The goal is to improve and combine the use of oncolytic viruses with immune checkpoint inhibitors to achieve a more potent immune response. First, cancer-specific viruses will be engineered so that they specifically target and destroy tumor cells and also reprogram the low nutrient immune suppressive conditions of the tumor microenvironment with the hope of enabling immune cells to function properly. Next, the oncolytic viruses will be combined with drugs that inhibit an immune checkpoint called PD-1 to see if the combination produces a magnified effect. These new, metabolism-targeting viruses, alone and in combination with checkpoint inhibitors, will be tested against melanoma in laboratory mice with the hope of bringing these new therapeutic approaches to patients in the future.

Updated: May 2016