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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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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.
