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Photocaged Cytokines for Cancer Immunotherapy
Emory University
Protein
Oncology
Hit To Lead or Lead Optimization
• The light-sensitive cage enables spatiotemporal activation of these cytokines (IL-2, IL12, IL-15).
• Emory inventors have engineered a new class of cytokines that enable spatiotemporal activation of therapeutic cytokines in response to external light exposure. In nature, some cytokines are expressed in a latent form (“shielded”) and remain dormant until a specific condition is triggered. The triggering event leads to activation of these cytokines by “de-shielding” and specific signaling pathways are then activated.
• Therapeutically promising cytokines IL-2, IL12, IL-15 are not expressed in a latent form and known to have poor circulation due to their small size and rapid clearance. The light-sensitive cage enables spatiotemporal activation of these cytokines. Signaling pathways can be activated by exposing these light sensitive cytokines to a light source (with specific wavelength – 356 nm (blue) and NIR (730 nm, more clinically relevant light wavelength – pulse oximeter, etc).
• “Caged structure” is also just large enough to be above the renal clearance cutoff, leading to prolonged circulation and the observation of less prevalent or severe toxic side effects. These photokines are rapidly triggered, highly color selective, and their activity can be spatially constrained with micrometer-scale resolution.
US20220305124A1
Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency. Biomacromolecules. (2020)
