Lacey Birnbaum
BME PhD Defense Presentation

Date: 2022-08-30
Time: 2 pm
Location / Meeting Link: HSRB E282, Zoom https://emory.zoom.us/j/94213659394?pwd=bi95RDZRWWJjVWljd29XTlQwSWR4UT09 Meeting ID: 942 1365 9394 Passcode: 282189

Committee Members:
Dr. Erik C. Dreaden (advisor); Dr. Gabriel Kwong; Dr. Gregory B. Lesinski (Emory); Dr. Wilbur Lam; Dr. Sarwish Rafiq (Emory)


Title: Development of optically responsive cytokine cancer immunotherapies

Abstract:
Cytokines are powerful immune modulatory proteins that have demonstrated therapeutic utility in both cancer and auto-immune disease therapy. For example, interleukin-2 (IL-2) therapy can induce complete and durable responses in a subset of patients with advanced cancer (metastatic melanoma and metastatic renal cell carcinoma). However, IL-2, and other pro-inflammatory cytokines often suffer from poor pharmacokinetics and high toxicity that limits their clinical effectiveness. To address these limitations, we have engineered prodrug variants of immuno-stimulatory cytokines that are reversibly inactivated via chemical modification with photo-labile polymers. Wavelength-specific light exposure restores the receptor binding ability of these "photo-cytokines", thus modulating their activity on immune cells by several orders of magnitude. We first establish that photo-labile polymer modification enables visible photon-dependent control of antigen-specific immune responses ex vivo and extends cytokine pharmacokinetics in vivo. Next, using photo-cytokines that differentially respond to visible and near-infrared light, we demonstrate Boolean logic based upon drug-induced T cytolytic activity and multicolor light exposure. Lastly, we show light-guided cytokine activation enhances CAR T cell therapy in vitro and that photo-cytokines can be controllably activated in vivo. These studies establish a set of light activatable tools in which to better understand and treat immune dysfunction-driven diseases including cancer.