Universiteit Leiden

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Proefschrift

Click-to-release for immune cell activation

This work describes the use of click-to-release chemistry to get spatiotemporal control over immunocytokine activity. Until now, immunocytokines (cytokines coupled to a tumor-targeting-moiety) remained active throughout the body, being able to bind their respective receptors, causing mild to severe side-effects in cancer patients.

Auteur
A. Barendrecht
Datum
13 februari 2024
Links
Thesis in Leiden Repository

Attempts have been made to improve the specific action of these immunocytokines, but these solutions remained very cytokine-specific and toxicity was not reduced significantly. Click-to-release chemistry allows us to inactivate a cytokine by blocking its free amines, present in lysines. This prevents the cytokine, IL-1β and TNF-α in particular, from binding its receptor. Removal of the blocking agent using a tetrazine restores the native amine and for IL-1β also its activity. By coupling the blocked cytokine to a targeting moiety allows for transport to the target, the tumor(-environment) upon which the unblocking or decaging can take place. This blocking-unblocking or caging-decaging was assessed using various cell-based assay. This technique can provide new opportunities in the immunocytokine field, as it is not cytokine-specific, and thereby opportunities in cancer therapy development.

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