Andrew Oberst, PhD, Technology Impact Award Recipient University of Washington Area of Research: All Cancers The goal of most cancer immunotherapies is to enable “killer” T cells to eliminate tumor cells. In doing this, checkpoint immunotherapies seek to engage the arm of the immune system that evolved to combat viral infection, and unleash it on tumor cells rather than on infected cells. However, the effectiveness of this approach is often blunted by the immunosuppressive environment that is found within solid tumors. Recently, Dr. Oberst found that introducing modified cells—in which anti-viral immune pathways were activated—into tumors was able to re-polarize tumor-associated immune cells and enhance their anti-cancer activity. By manipulating immune pathways to “trick” these cells into producing key cytokines associated with viral infection, the tumor microenvironment could be re-programmed to more closely resemble a site of viral infection, thereby unleashing the killing activity of the immune system. Now, Dr. Oberst plans to expand and improve this approach by using protein engineering to create versions of key antiviral innate immune signaling proteins and then deploy these proteins by either directly expressing them within the cells of the tumor microenvironment, or by using them to “arm” tumor-homing T cells, which will accumulate within tumors and promote control of tumor growth. This latter strategy will thereby repurpose T cells as “immune bombs,” capable of skewing the immune landscape within tumors away from the immunosuppressive milieu that prevents effective immunotherapy, and instead toward the immune functions that can control tumor growth long-term. Projects and Grants Re-Programming the Immunological State of the Tumor Microenvironment Using Engineered Innate Immune Proteins University of Washington | All Cancers | 2020 Inducing Immunogenic Cell Death to Improve Cancer Immunotherapy University of Washington | All Cancers | 2018
