Light-responsive cytokine prodrugs with controlled activation for improved cancer immunotherapy.
- Prolonged circulation and biased immune cell-selectivity.
- Controlled local activation, reduces off-target toxicity.
- Requires less frequent dosing.
While recombinant cytokines hold great potential for cancer immunotherapy, their clinical use has greatly declined in recent years. Their off-target toxicity/pleiotropic effects and poor circulation are major issues and challenging to control. There is a need to develop improved cytokines therapy with no or less side effects and improved circulation to eliminate the need of frequent and high dosing.
Emory inventors have engineered a new class of cytokines that enable tissue-restricted activation in response to external light exposure. These light-activatable cytokines consists of an immune modulatory protein to which a chemical linker is appended that allows for further attachment of a polymer, both or one of which alter or block normal protein activity and extend the duration of blood circulation. In response to exposure with light of the appropriate wavelength, the linker and/or polymer fragment alters or recovers the activity of the pro-drug (or caged) protein. These photokines are rapidly triggered, highly color selective, and their activity can be spatially constrained with micrometer-scale resolution. In vivo experiments showed 11-fold increase in circulation half-life in C57BL/6 mice after the tail injection of scIL-12. Prolonged circulation and improved tumor accumulation may necessitate less frequent dosing and the observation of less prevalent or severe toxic side effects.
In vivo testing for size, binding affinity and half-life performed.
Publications: Perdue, L. A. et al. (2020). Biomacromolecules.
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